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412 results on '"Neuroendocrinologie cellulaire et moléculaire"'

1. Short erythropoietin-derived peptide enhances memory, improves long-term potentiation, and counteracts amyloid beta–induced pathology

Author

Oksana Dmytriyeva, Stanislava Pankratova, David P.D. Woldbye, Laurent Bezin, Katia Soud, Casper René Gøtzsche, Amor Belmeguenai, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Aging, Amyloid beta, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Long-Term Potentiation, Neuronal Outgrowth, Morris water navigation task, Hippocampus, Pharmacology, Neuroprotection, Rats, Sprague-Dawley, 03 medical and health sciences, 0302 clinical medicine, Memory, medicine, Animals, Rats, Wistar, Erythropoietin, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, Amyloid beta-Peptides, biology, business.industry, General Neuroscience, Neurodegeneration, Neurodegenerative Diseases, Long-term potentiation, medicine.disease, Neuroprotective Agents, 030104 developmental biology, Gliosis, biology.protein, Dementia, Female, Neurology (clinical), Geriatrics and Gerontology, medicine.symptom, Peptides, business, 030217 neurology & neurosurgery, Developmental Biology, medicine.drug
Abstract

Neurodegenerative disorders such as Alzheimer's disease (AD) are characterized by the irreversible neuronal loss and memory impairment, and current treatments are merely symptomatic. Erythropoietin (EPO) has been shown to possess neurotrophic, neuroprotective, anti-inflammatory, and memory-enhancing effects, which could be therapeutically beneficial in the different aspects of AD. However, the hematopoietic effect of EPO has hampered its potential as a neuroprotective and procognitive agent. In this study, we characterized a novel small peptide, NL100, derived from a conserved C-helix region of EPO. NL100 was shown to bind to the EPO receptor, induce neuritogenesis, and protect hippocampal neurons from oxidative- and Aβ25-35-induced neurodegeneration in vitro. Importantly, long-term NL100 treatment did not induce hematopoiesis, overcoming this challenge associated with EPO. Memory-enhancing effects were demonstrated after NL100 treatment in social recognition test for short-term memory, in both healthy rats and rats challenged centrally with Aβ25-35 peptide, and in the Morris water maze test for spatial memory. Moreover, NL100 was shown to reverse Aβ25-35-induced hippocampal degeneration and gliosis as well as pilocarpine-induced suppression of long-term potentiation in rats. In conclusion, NL100 is a novel EPO-derived nonhematopoietic peptide with neuroprotective and memory-enhancing effects and could therefore be a potential candidate for the development of new treatments for neurodegenerative disorders and dementia.

Published
2019
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2. Dysregulation of Aldosterone Secretion in Mast Cell–Deficient Mice

Author

Estelle Louiset, Hervé Lefebvre, Arnaud Arabo, Céline Duparc, Isabelle Boutelet, Hadrien-Gaël Boyer, Julien Wils, Sylvie Renouf, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), and Neuroendocrinologie cellulaire et moléculaire

Subjects
Male, 0301 basic medicine, MESH: Renin, mast cells, MESH: Adrenal Cortex Neoplasms, Adrenocortical adenoma, chemistry.chemical_compound, Primary aldosteronism, Renin, MESH: Animals, Aldosterone, renin–angiotensin system, Mice, Inbred BALB C, MESH: Mast Cells, Diet, Sodium-Restricted, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Mast cell, Hyperaldosteronism, MESH: Hyperaldosteronism, MESH: Neoplasms, Experimental, medicine.anatomical_structure, Adrenocortical Adenoma, Female, MESH: Adrenocortical Adenoma, medicine.medical_specialty, hypertension, mice, food.diet, MESH: Mice, Inbred BALB C, Biology, Low sodium diet, Mast cell proliferation, 03 medical and health sciences, food, MESH: Mice, Inbred C57BL, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Internal medicine, Renin–angiotensin system, Internal Medicine, medicine, Animals, MESH: Mice, MESH: Aldosterone, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Neoplasms, Experimental, medicine.disease, Adrenal Cortex Neoplasms, MESH: Male, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, adrenal, chemistry, MESH: Diet, Sodium-Restricted, hyperaldosteronism, low-sodium diet, MESH: Female
Abstract

Resident adrenal mast cells have been shown to activate aldosterone secretion in rat and man. Especially, mast cell proliferation has been observed in adrenal tissues from patients with aldosterone-producing adrenocortical adenoma. In the present study, we show that the activity of adrenal mast cells is stimulated by low-sodium diet and correlates with aldosterone synthesis in C57BL/6 and BALB/c mice. We have also investigated the regulation of aldosterone secretion in mast cell–deficient C57BL/6 Kit W-sh/W-sh mice in comparison with wild-type C57BL/6 mice. Kit W-sh/W-sh mice submitted to normal sodium diet had basal plasma aldosterone levels similar to those observed in wild-type animals. Conversely, low-sodium diet unexpectedly induced an exaggerated aldosterone response, which seemed to result from an increase in adrenal renin and angiotensin type 1 receptor expression. Severe hyperaldosteronism was associated with an increase in systolic blood pressure and marked hypokalemia, which favored polyuria. Adrenal renin and angiotensin type 1 receptor overexpression may represent a compensatory mechanism aimed at activating aldosterone production in the absence of mast cells. Finally, C57BL/6 Kit W-sh/W-sh mice represent an unexpected animal model of primary aldosteronism, which has the particularity to be triggered by sodium restriction.

Published
2017
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3. THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein-coupled receptors

Author

Alexander, Stephen PH, Christopoulos, Arthur, Davenport, Anthony P, Kelly, Eamonn, Mathie, Alistair, Peters, John A, Veale, Emma L, Armstrong, Jane F, Faccenda, Elena, Harding, Simon D, Pawson, Adam J, Sharman, Joanna L, Southan, Christopher, Davies, Jamie A, Arumugam, Thiruma V, Bennett, Andrew, Sjogren, Benita, Sobey, Christopher, Wong, Szu Shen, Abbracchio, Maria P, Alexander, Wayne, Al-hosaini, Khaled, Back, Magnus, Beaulieu, Jean-Martin, Bernstein, Kenneth E, Bettler, Bernhard, Birdsall, Nigel JM, Blaho, Victoria, Bousquet, Corinne, Brauner-Osborne, Hans, Burnstock, Geoffrey, Calo, Girolamo, Castano, Justo P, Catt, Kevin J, Ceruti, Stefania, Chazot, Paul, Chiang, Nan, Chun, Jerold, Cianciulli, Antonia, Clapp, Lucie H, Couture, Rejean, Csaba, Zsolt, Dent, Gordon, Singh, Khuraijam Dhanachandra, Douglas, Steven D, Dournaud, Pascal, Eguchi, Satoru, Escher, Emanuel, Filardo, Edward, Fong, Tung M, Fumagalli, Marta, Gainetdinov, Raul R, de Gasparo, Marc, Gershengorn, Marvin, Gobeil, Fernand, Goodfriend, Theodore L, Goudet, Cyril, Gregory, Karen J, Gundlach, Andrew L, Hamann, Jorg, Hanson, Julien, Hauger, Richard L, Hay, Debbie, Heinemann, Akos, Hollenberg, Morley D, Holliday, Nicholas D, Horiuchi, Mastgugu, Hoyer, Daniel, Hunyady, Laszlo, Husain, Ahsan, Ijzerman, Adriaan P, Inagami, Tadashi, Jacobson, Kenneth A, Jensen, Robert T, Jockers, Ralf, Jonnalagadda, Deepa, Karnik, Sadashiva, Kaupmann, Klemens, Kemp, Jacqueline, Kennedy, Charles, Kihara, Yasuyuki, Kozielewicz, Pawel, Kreienkamp, Hans-Juergen, Kukkonen, Jyrki P, Langenhan, Tobias, Leach, Katie, Lecca, Davide, Lee, John D, Leeman, Susan E, Leprince, Jerome, Lolait, Stephen J, Lupp, Amelie, Macrae, Robyn, Maguire, Janet, Mazella, Jean, McArdle, Craig A, Melmed, Shlomo, Michel, Martin C, Miller, Laurence, Mitolo, Vincenzo, Mouillac, Bernard, Murphy, Philip M, Nahon, Jean-Louis, Norel, Xavier, Nyimanu, Duuamene, O'Carroll, Anne-Marie, Offermanns, Stefan, Panaro, Maria A, Pertwee, Roger G, Pin, Jean-Philippe, Prossnitz, Eric, Ramachandran, Rithwik, Reinscheid, Rainer K, Rondard, Philippe, Rovati, G Enrico, Ruzza, Chiara, Sanger, Gareth, Schoeneberg, Torsten, Schulte, Gunnar, Schulz, Stefan, Segaloff, Deborah L, Serhan, Charles N, Stoddart, Leigh A, Sugimoto, Yukihiko, Summers, Roger, Tan, Valerie, Thomas, Walter, Timmermans, Pieter BMWM, Tirupula, Kalyan, Tulipano, Giovanni, Unal, Hamiyet, Unger, Thomas, Vanderheyden, Patrick, Vaudry, David, Vaudry, Hubert, Vilardaga, Jean-Pierre, Walker, Christopher S, Ward, Donald T, Wester, Hans-Juergen, Willars, Gary B, Williams, Tom Lloyd, Woodruff, Trent M, Yao, Chengcan, Aldrich, Richard W, Becirovic, Elvir, Biel, Martin, Catterall, William A, Conner, Alex C, Davies, Paul, Delling, Markus, Di Virgilio, Francesco, Falzoni, Simonetta, George, Chandy, Goldstein, Steve AN, Grissmer, Stephan, Ha, Kotdaji, Hammelmann, Verena, Hanukoglu, Israel, Jarvis, Mike, Jensen, Anders A, Kaczmarek, Leonard K, Kellenberger, Stephan, King, Brian, Lynch, Joseph W, Perez-Reyes, Edward, Plant, Leigh D, Rash, Lachlan D, Ren, Dejian, Sivilotti, Lucia G, Smart, Trevor G, Snutch, Terrance P, Tian, Jinbin, Van den Eynde, Charlotte, Vriens, Joris, Wei, Aguan D, Winn, Brenda T, Wulff, Heike, Xu, Haoxing, Yue, Lixia, Zhang, Xiaoli, Zhu, Michael, Coons, Laurel, Fuller, Peter, Korach, Kenneth S, Young, Morag, Bryant, Clare, Farndale, Richard W, Hobbs, Adrian, Jarvis, Gavin E, MacEwan, David, Monie, Tom P, Waldman, Scott, Beuve, Annie, Boison, Detlev, Brouckaert, Peter, Burnett, John C, Burns, Kathryn, Dessauer, Carmen, Friebe, Andreas, Garthwaite, John, Gertsch, Jurg, Helsby, Nuala, Izzo, Angelo A, Koesling, Doris, Kuhn, Michaela, Ostrom, Rennolds, Papapetropoulos, Andreas, Potter, Lincoln R, Pyne, Nigel J, Pyne, Susan, Russwurm, Michael, Schmidt, Harald HHW, Seifert, Roland, Stasch, Johannes-Peter, Szabo, Csaba, van der Stelt, Mario, van der Vliet, Albert, Watts, Val, Anderson, Catriona MH, Broer, Stefan, Dawson, Paul, Hagenbuch, Bruno, Hammond, James R, Hancox, Jules, Inui, Ken-ichi, Kanai, Yoshikatsu, Kemp, Stephan, Thwaites, David T, Verri, Tiziano, University of Nottingham, UK (UON), Monash university, University of Cambridge [UK] (CAM), University of Bristol [Bristol], University of Greenwich, Ninewells Hospital and Medical School [Dundee], University of Edinburgh, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de médecine moléculaire de Rangueil (I2MR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR150-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Drug Design and Pharmacology [Copenhagen] (ILF), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), University of Córdoba [Córdoba], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Novartis Institutes for BioMedical Research (NIBR), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), ARVALIS - Institut du végétal [Paris], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Glaxo Smith Kline [Harlow], University of Antwerp (UA), Neuroendocrinologie cellulaire et moléculaire, European Synchrotron Radiation Facility (ESRF), Experimental Medicine and Immunotherapeutics [Cambridge, UK], Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University [Riyadh] (KSU), Department of Cardiology, Karolinska University Hospital, Karolinska Institutet [Stockholm], Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Medical Sciences, Università degli Studi di Ferrara (UniFE), Department of Pharmacological Sciences and Biomolecular, University of Milan, Department of Molecular Biology Helen L. Dorris, The Scripps Research Institute, Département de Physiologie, Université de Montréal (UdeM), Department of Pharmacology, Université de Sherbrooke (UdeS), Departments of Physiology & Pharmacology, and Medicine [Calgary, Canada] (School of Medicine), University of Calgary, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute of Biochemistry, Medical Faculty, University of Leipzig, Department of Molecular and Biochemical Pharmacology, and Pleinlaan 2

Subjects
0301 basic medicine, RM, Databases, Pharmaceutical, Computer science, Drug classification, Pharmacology, Ligands, Receptors, G-Protein-Coupled, NO, law.invention, 03 medical and health sciences, Databases, G-Protein-Coupled, 0302 clinical medicine, law, Summary information, Receptors, Animals, Humans, Pharmacology & Pharmacy, The Concise Guide to Pharmacology 2019/20, ComputingMilieux_MISCELLANEOUS, G protein-coupled receptor, Clinical pharmacology, Science & Technology, Extramural, POTENT, Pharmaceutical Preparations, 3. Good health, 030104 developmental biology, Pharmaceutical, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Catalytic receptors, Life Sciences & Biomedicine, 030217 neurology & neurosurgery
Abstract

© 2019 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of The British Pharmacological Society. The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14748. G protein-coupled receptors are one of the six major pharmacological targets into which the Guide is divided, with the others being: ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2019
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4. Glutamate controls vessel-associated migration of GABA interneurons from the pial migratory route via NMDA receptors and endothelial protease activation

Author

Léger, Cécile, Dupré, Nicolas, Aligny, Caroline, Bénard, Magalie, Lebon, Alexis, Henry, Vincent, Hauchecorne, Michelle, Galas, Ludovic, Frebourg, Thierry, Leroux, Philippe, Vivien, Denis, Lecointre, Maryline, Marret, Stéphane, Gonzalez, Bruno J., Team 4 'NeoVasc' - INSERM U1245, Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Endothélium microcirculatoire cérébral et lésions du système nerveux central au cours du développement (Néovasc), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Néonatalogie [Hôpital des enfants Toulouse], Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Lab Phys Collis Electron & Atom, Université de Brest (UBO), Neuroendocrinologie cellulaire et moléculaire, GIP Cyceron (Cyceron), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Team 4 NeoVasc - Region Team ERI 28 INSERM (Neovasc), Service Obstétrique [CHU Toulouse], Pôle Femme-Mère-Couple [CHU Toulouse], and Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)

Subjects
Endothelial cells, Neurogenesis, [SDV]Life Sciences [q-bio], Glutamic Acid, Mice, Transgenic, Receptors, N-Methyl-D-Aspartate, GABA interneuron, Mice, Cell Movement, Interneurons, Animals, Humans, GABAergic Neurons, Migration, gamma-Aminobutyric Acid, ComputingMilieux_MISCELLANEOUS, Brain Mapping, Glutamate Decarboxylase, Somatosensory Cortex, NMDAR, nervous system, Animals, Newborn, Gene Expression Regulation, Matrix Metalloproteinase 9, t-PA, Tissue Plasminogen Activator, Blood Vessels, Original Article, MMP-9
Abstract

During cortex development, fine interactions between pyramidal cells and migrating GABA neurons are required to orchestrate correct positioning of interneurons, but cellular and molecular mechanisms are not yet clearly understood. Functional and age-specific expression of NMDA receptors by neonate endothelial cells suggests a vascular contribution to the trophic role of glutamate during cortical development. Associating functional and loss-of-function approaches, we found that glutamate stimulates activity of the endothelial proteases MMP-9 and t-PA along the pial migratory route (PMR) and radial cortical microvessels. Activation of MMP-9 was NMDAR-dependent and abrogated in t-PA−/− mice. Time-lapse recordings revealed that glutamate stimulated migration of GABA interneurons along vessels through an NMDAR-dependent mechanism. In Gad67-GFP mice, t-PA invalidation and in vivo administration of an MMP inhibitor impaired positioning of GABA interneurons in superficial cortical layers, whereas Grin1 endothelial invalidation resulted in a strong reduction of the thickness of the pial migratory route, a marked decrease of the glutamate-induced MMP-9-like activity along the PMR and a depopulation of interneurons in superficial cortical layers. This study supports that glutamate controls the vessel-associated migration of GABA interneurons by regulating the activity of endothelial proteases. This effect requires endothelial NMDAR and is t-PA-dependent. These neurodevelopmental data reinforce the debate regarding safety of molecules with NMDA-antagonist properties administered to preterm and term neonates. Electronic supplementary material The online version of this article (10.1007/s00018-019-03248-5) contains supplementary material, which is available to authorized users.

Published
2019
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5. Reversal of a Blunted Follicle-Stimulating Hormone by Chemotherapy in an Inhibin B–Secreting Adrenocortical Carcinoma

Author

Najiba Lahlou, Stéphanie Espiard, Estelle Louiset, Bertrand Dousset, Marie Bienvenu, Mathilde Sibony, Lionel Groussin, Jérôme Bertherat, Rossella Libé, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biologie hormonale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Saint-Vincent de Paul, Service d'anatomie pathologique [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), [Institut Cochin] Département Endocrinologie, métabolisme, diabète (EMD) (EMD), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de gynécologie et d'endocrinologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Saint-Vincent de Paul, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, endocrine system, Endocrinology, Diabetes and Metabolism, education, 030209 endocrinology & metabolism, Gonadotropin-releasing hormone, Case Reports, inhibin B, 03 medical and health sciences, Follicle-stimulating hormone, Cushing syndrome, 0302 clinical medicine, Internal medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, adrenocortical carcinoma, Adrenocortical carcinoma, Mitotane, Adrenal, business.industry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, 3. Good health, Endocrinology, 030220 oncology & carcinogenesis, tumor marker, business, Luteinizing hormone, Immunostaining, hormones, hormone substitutes, and hormone antagonists, Hormone, medicine.drug
Abstract

Context: Adrenocortical carcinomas (ACCs) are revealed in 60% of cases by steroid hypersecretion. Alternatively, it is uncommon to observe a paraneoplastic syndrome due to a peptide oversecretion. Case Description: We describe a 60-year-old man with a right adrenal mass. Hormonal evaluation showed an ACTH-independent Cushing syndrome. Surprisingly, follicle-stimulating hormone (FSH) levels were suppressed and blunted during gonadotropin-releasing hormone stimulation, despite normal luteinizing hormone levels. Levels of inhibin B, which negatively regulates the pituitary FSH, were very high. Given the atypical hormonal findings, an adrenal mass biopsy was performed, which allowed the diagnosis of an adrenocortical tumor (positive for steroidogenic factor-1 immunostaining). Moreover, an intense α-inhibin subunit immunostaining was observed. Because of the presence of metastases, the patient received mitotane and chemotherapy (etoposide and cisplatin). After 2 cycles, the inhibin B dropped. After 5 cycles, tumor size was reduced by 15%. Inhibin B levels remained low, and basal and gonadotropin-releasing hormone–stimulated FSH levels normalized. The patient underwent tumor resection, and pathology confirmed the ACC diagnosis (Weiss score of 9). The intensity of the α-inhibin subunit immunostaining was significantly decreased. Conclusions: We report the case of an inhibin B–secreting ACC in which the response to chemotherapy and mitotane was associated with a normalization of inhibin B secretion, allowing the reversal of the blunted FSH secretion. Inhibin B should be measured in case of suppressed FSH levels despite normal luteinizing hormone levels and may be considered a tumoral marker in some ACCs, even during treatment follow-up., Precis: We studied an adrenal mass with suppressed FSH levels, blunted after GnRH stimulation, and found an inhibin B–secreting adrenocortical carcinoma, in which inhibin B was normalized after chemotherapy.

Published
2017
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6. Consequences of acclimation on the resistance to acute thermal stress: Proteomic focus on mussels from pristine site

Author

Romain Péden, Agnès Poret, Béatrice Rocher, Philippe Chan, Stéphanie Olivier, Florence Bultelle, David Vaudry, Frank Le Foll, Stress Environnementaux et BIOsurveillance des milieux aquatiques (SEBIO), Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Reims Champagne-Ardenne (URCA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), Sciences Appliquées à L'Environnement (SCALE), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), and Normandie Université (NU)

Subjects
Proteomics, 0106 biological sciences, 0301 basic medicine, Hot Temperature, animal structures, Proteome, Acclimatization, [SDE.MCG]Environmental Sciences/Global Changes, Intertidal zone, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Aquatic Science, Biology, Oceanography, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Heat shock protein, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Animals, 14. Life underwater, ComputingMilieux_MISCELLANEOUS, Mytilus, Resistance (ecology), Ecology, fungi, General Medicine, biology.organism_classification, Pollution, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, 13. Climate action, [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, Microcosm, Anaerobic exercise, Blue mussel, Environmental Monitoring
Abstract

Climate change constitutes an additional threat for intertidal species that already have to cope with a challenging environment. The present study focuses on the blue mussel Mytilus edulis and aims at investigating the importance of thermal acclimation in heat stress response. Microcosm exposures were performed with mussels submitted to an identical acute thermal stress following two thermal summer acclimations standing for present or future temperature conditions. Gill proteomes were analyzed by 2DE and 96 differentially expressed proteoforms were identified. Our results show that cell integrity appears to be maintained by the rise in molecular protective systems (i.e. Heat Shock Proteins), and by the reallocation of energy production via a switch to anaerobic metabolism and the setting up of alternative energy pathways. Finally, our results indicate that the response of mussels to acute thermal stress is conditioned by the acclimation temperature with an improved response in organisms acclimated to higher temperatures.

Published
2016
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7. The neuropeptide 26RFa (QRFP) is a key regulator of glucose homeostasis and its activity is markedly altered in obese/hyperglycemic mice

Author

Nicolas Chartrel, Youssef Anouar, Hervé Lefebvre, Marie-Anne Le Solliec, Jérôme Leprince, Anneli Nordqvist, Gaëtan Prévost, Valéry Brunel, Mouna El Mehdi, Julie Maucotel, Emmanuelle Nédélec, Pierre Déchelotte, Moïse Coëffier, Hind Berrahmoune, Alexandre Benani, Justine Bons, Arnaud Arabo, Saloua Cherifi, Marie Christine Picot, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'endocrinologie, diabétologie et maladies métaboliques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), AstraZeneca, Laboratoire de biochimie générale [Rouen], Normandie Université (NU)-Centre hospitalier universitaire de Rouen, This work was funded by INSERM (U1239), the University of Rouen, the Institute for Research and Innovation in Biomedecine (IRIB), the 'Fondation pour la Recherche Médicale' (DEA 20140629966), the 'Société Francophone du Diabète' (R16038EE) and the 'Plateforme Régionale de Recherche en Imagerie Cellulaire de Normandie (PRIMACEN)'. The present study was also co-funded by European Union and Normandie Regional Council. Europe gets involved in Normandie with European Regional Development Fund (ERDF)., Psychologie et Neurosciences de la Cognition et de l'affectivité (PSY-NCA), Normandie Université (NU)-Normandie Université (NU), Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Neuroendocrinologie cellulaire et moléculaire, and chartrel, nicolas

Subjects
Blood Glucose, Male, obesity, Physiology, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Regulator, Mice, Obese, 26RFa, Mice, 0302 clinical medicine, Glucose homeostasis, Homeostasis, Insulin, glucose, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, 0303 health sciences, diabetes, Chemistry, incretin, [SDV] Life Sciences [q-bio], obésité, Alimentation et Nutrition, Carbohydrate Metabolism, diabète, medicine.medical_specialty, Neuropeptide, Incretin, 030209 endocrinology & metabolism, 03 medical and health sciences, Physiology (medical), Diabetes mellitus, Internal medicine, medicine, Animals, Humans, glucose homeostasis, Food and Nutrition, 030304 developmental biology, homéostasie, Neuropeptides, Increasing insulin, QRFP, Neurosciences, Glucose Tolerance Test, medicine.disease, Mice, Inbred C57BL, Endocrinology, Hyperglycemia, Neurons and Cognition
Abstract

International audience; Recent studies have shown that the hypothalamic neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin, and increasing insulin sensitivity. In this study, we further characterized the role of the 26RFa/GPR103 peptidergic system in the global regulation of glucose homeostasis using a 26RFa receptor antagonist, and also assessed whether a dysfunction of the 26RFa/GPR103 system occurs in obese hyperglycemic mice. Firstly, we demonstrate that administration of the GPR103 antagonist reduces the global glucose-induced incretin effect and insulin sensitivity whereas, conversely, administration of exogenous 26RFa attenuates glucose-induced hyperglycemia. Using a mouse model of high-fat diet-induced obesity and hyperglycemia, we found a loss of the anti-hyperglcemic effect and insulinotropic activity of 26RFa, accompanied with a marked reduction of its insulin-sensitive effect. Interestingly, this resistance to 26RFa is associated with a down-regulation of the 26RFa receptor in the pancreatic islets, and insulin target tissues. Finally, we observed that the production and release kinetics of 26RFa after an oral glucose challenge is profoundly altered in the high-fat mice. Altogether, the present findings support the view that 26RFa is a key regulator of glucose homeostasis whose activity is markedly altered under obese/hyperglycemic conditions.

Published
2019
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8. The neuropeptide 26RFa in the human gut and pancreas: potential involvement in glucose homeostasis

Author

Nicolas Chartrel, Marie-Anne Le Solliec, Françoise Gobet, Hind Berrahmoune, Valéry Brunel, Mouna El Mehdi, Saloua Cherifi, Youssef Anouar, Marie Christine Picot, Gaëtan Prévost, Alexandre Benani, Emmanuelle Nédélec, Arnaud Arabo, Jérôme Leprince, Hervé Lefebvre, Prévost, Gaëtan, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'endocrinologie, diabétologie et maladies métaboliques [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Laboratoire de biochimie générale [Rouen], Normandie Université (NU)-Centre hospitalier universitaire de Rouen, This work was funded by INSERM (U1239), the University of Rouen, the Institute for Research and Innovation in Biomedecine (IRIB), the 'Fondation pour la Recherche Médicale' (DEA 20140629966), the 'Société Francophone du Diabète' (R16038EE) and the 'Plateforme Régionale de Recherche en Imagerie Cellulaire de Normandie (PRIMACEN)'. The present study was also co-funded by European Union and Normandie Regional Council. Europe gets involved in Normandie with European Regional Development Fund (ERDF)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Psychologie et Neurosciences de la Cognition et de l'affectivité (PSY-NCA), Service d'Anatomie et Cytologie Pathologique [Rouen], Neuroendocrinologie cellulaire et moléculaire, Hôpital Charles Nicolle [Rouen], and chartrel, nicolas

Subjects
0301 basic medicine, medicine.medical_specialty, insulin, obesity, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Incretin, pancréas, 030209 endocrinology & metabolism, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Insulin resistance, intestin, Gastric glands, Internal medicine, Internal Medicine, Medicine, Glucose homeostasis, glucose homeostasis, Food and Nutrition, gut, pancreas, incretin, glucose, ComputingMilieux_MISCELLANEOUS, insuline, homéostasie, lcsh:RC648-665, business.industry, Research, Stomach, Pancreatic islets, Insulin, digestive, oral, and skin physiology, Neurosciences, medicine.disease, [SDV] Life Sciences [q-bio], obésité, 030104 developmental biology, medicine.anatomical_structure, Neurons and Cognition, Alimentation et Nutrition, business, Pancreas
Abstract

Objective Recent studies performed in mice revealed that the neuropeptide 26RFa regulates glucose homeostasis by acting as an incretin and by increasing insulin sensitivity. However, in humans, an association between 26RFa and the regulation of glucose homeostasis is poorly documented. In this study, we have thus investigated in detail the distribution of 26RFa and its receptor, GPR103, in the gut and the pancreas, and determined the response of this peptidergic system to an oral glucose challenge in obese patients. Design and methods Distribution of 26RFa and GPR103 was examined by immunohistochemistry using gut and pancreas tissue sections. Circulating 26RFa was determined using a specific radioimmunoassay in plasma samples collected during an oral glucose tolerance test. Results 26RFa and GPR103 are present all along the gut but are more abundant in the stomach and duodenum. In the stomach, the peptide and its receptor are highly expressed in the gastric glands, whereas in the duodenum, ileum and colon they are present in the enterocytes and the goblet cells. In the pancreatic islets, the 26RFa/GPR103 system is mostly present in the β cells. During an oral glucose tolerance test, plasma 26RFa profile is different between obese patients and healthy volunteers, and we found strong positive correlations between 26RFa blood levels and the BMI, and with various parameters of insulin secretion and insulin resistance. Conclusion The present data suggest an involvement of the 26RFa/GPR103 peptidergic system in the control of human glucose homeostasis.

Published
2019
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9. Antioxidant and Anti-Apoptotic Activity of Octadecaneuropeptide Against 6-OHDA Toxicity in Cultured Rat Astrocytes

Author

Marie-Christine Tonon, Olfa Masmoudi-Kouki, Jérôme Leprince, Yosra Hamdi, Hadhemi Kaddour, Fatma Amri, Seyma Bahdoudi, Hubert Vaudry, Sami Zekri, Sana Mezghani, Ibtissem Bouannee, David Vaudry, Mohamed Amri, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biological Sciences, Laboratory of Functional Neurophysiology and Pathology, Research Unit UR/11ES09, Faculty of Science of Tunis-Faculty of Science of Tunis-Université de Tunis El Manar (UTM), Université de Tunis El Manar (UTM), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Neuroendocrinologie cellulaire et moléculaire

Subjects
0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Apoptosis, 6-hydroxydopamine, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, medicine.disease_cause, Antioxidants, chemistry.chemical_compound, Octadecaneuropeptide, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cells, Cultured, Diazepam Binding Inhibitor, biology, Caspase 3, Neurodegeneration, hemic and immune systems, General Medicine, respiratory system, Catalase, Neuroprotection, Cell biology, Neuroprotective Agents, Cell death, Programmed cell death, Oxidative phosphorylation, Superoxide dismutase, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Animals, Rats, Wistar, Oxidopamine, Superoxide Dismutase, Neuropeptides, Glutathione, medicine.disease, Peptide Fragments, Rats, 030104 developmental biology, chemistry, nervous system, Oxidative stress, Astrocytes, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Reactive Oxygen Species, 030217 neurology & neurosurgery
Abstract

International audience; Oxidative stress, associated with various neurodegenerative diseases, promotes ROS generation, impairs cellular antioxidant defenses, and finally, triggers both neurons and astroglial cell death by apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide (ODN). We have previously reported that ODN acts as a potent neuroprotective agent that prevents 6-OHDA-induced apoptotic neuronal death. The purpose of the present study was to investigate the potential glioprotective effect of ODN on 6-OHDA-induced oxidative stress and cell death in cultured rat astrocytes. Incubation of astrocytes with graded concentrations of ODN (10-14 to 10-8 M) inhibited 6-OHDA-evoked cell death in a concentration- and time-dependent manner. In addition, ODN prevented the decrease of mitochondrial activity and caspase-3 activation induced by 6-OHDA. 6-OHDA-treated cells also exhibited enhanced levels of ROS associated with a generation of H2O2 and O2°-, and a reduction of both superoxide dismutase (SOD) and catalase (CAT) activities. Co-treatment of astrocytes with low concentrations of ODN dose-dependently blocked 6-OHDA-evoked production of ROS and inhibition of antioxidant enzyme activities. Concomitantly, ODN stimulated Mn-SOD, CAT, glutathione peroxidase-1, and sulfiredoxin-1 gene transcription and rescued 6-OHDA-associated reduced expression of endogenous antioxidant enzymes. Taken together, these data indicate that, in rat astrocytes, ODN exerts anti-apoptotic and anti-oxidative activities, and hence prevents 6-OHDA-induced oxidative assault and cell death. ODN is thus a potential candidate to delay neuronal damages in various pathological conditions involving oxidative neurodegeneration.

Published
2018
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10. AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress

Author

Youssef Anouar, Dorthe Cartier, Destiny-Love Manecka, Olivier Boyer, Abdallah Hamieh, Anne-Marie François-Bellan, Jérôme Leprince, Hugo Pothion, Houssni Abid, Sahil Adriouch, Isabelle Lihrmann, Christine Bucharles, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Institut de neurophysiopathologie (INP), and Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Transcription, Genetic, Cell Survival, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Cellular differentiation, Cell, Neuroscience (miscellaneous), PGC-1α, AMP-Activated Protein Kinases, Mitochondriogenesis, Models, Biological, PC12 Cells, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Neuroendocrine Cells, cAMP, Gene expression, medicine, Animals, Humans, Selenoproteins, ComputingMilieux_MISCELLANEOUS, Neuroendocrine cell, NRF-1, Chemistry, Nuclear Respiratory Factor 1, AMPK, Selenoprotein T, Cell Differentiation, Neuroendocrine cell differentiation, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Cell biology, Rats, Enzyme Activation, Oxidative Stress, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, Neurology, Mitochondrial biogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Pituitary Adenylate Cyclase-Activating Polypeptide, 030217 neurology & neurosurgery, Protein Binding
Abstract

International audience; Several cues including pituitary adenylate cyclase-activating polypeptide (PACAP), which acts through cAMP stimulation, specify the conversion of sympathoadrenal (SA) precursors toward different cell phenotypes by promoting their survival and differentiation. Selenoprotein T (SELENOT) is a PACAP-stimulated ER oxidoreductase that exerts an essential antioxidant activity and whose up-regulation is associated with SA cell differentiation. In the present study, we investigated the transcriptional cascade elicited by PACAP/cAMP to trigger SELENOT gene transcription during the conversion of PC12 cells from SA progenitor-like cells toward a neuroendocrine phenotype. Unexpectedly, we found that PACAP/cAMP recruits the canonical pathway that regulates mitochondrial function in order to elicit SELENOT gene transcription and the consequent antioxidant response during PC12 cell differentiation. This cascade involves LKB1-mediated AMPK activation in order to stimulate SELENOT gene transcription through the PGC1-α/NRF-1 complex, thus allowing SELENOT to promote PACAP-stimulated neuroendocrine cell survival and differentiation. Our data reveal that a PACAP and cAMP-activated AMPK-PGC-1α/NRF-1 cascade is critical for the coupling of oxidative stress tolerance, via SELENOT gene expression, and mitochondrial biogenesis in order to achieve PC12 cell differentiation. The data further highlight the essential role of SELENOT in cell metabolism during differentiation.

Published
2018
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11. Different Dose-Dependent Modes of Action of C-Type Natriuretic Peptide on Pseudomonas aeruginosa Biofilm Formation

Author

Thomas Clamens, Jérôme Leprince, Ali Tahrioui, Sophie Rodrigues, Olivier Lesouhaitier, Jérémy Enault, Lucille Roquigny, Alexis Bazire, Alain Dufour, Sylvie Chevalier, Thibaut Rosay, Florie Desriac, Laure Taupin, Marc G. J. Feuilloley, Emeline Bouffartigues, Pierre-Jean Racine, Laboratoire de Microbiologie Signaux et Microenvironnement (LMSM), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Laboratoire de Biotechnologie et Chimie Marines (LBCM), Université de Bretagne Sud (UBS)-Université de Brest (UBO)-Institut Universitaire Européen de la Mer (IUEM), Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Microbiologie du Froid – Signaux et Micro-Environnement (LMDF-SME), and Neuroendocrinologie cellulaire et moléculaire

Subjects
0301 basic medicine, Microbiology (medical), medicine.drug_class, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, 030106 microbiology, bacterial adaptation, lcsh:Medicine, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Bacterial growth, medicine.disease_cause, biofilm, lung, cystic fibrosis, 03 medical and health sciences, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Membrane fluidity, medicine, Natriuretic peptide, Immunology and Allergy, Mode of action, Molecular Biology, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, General Immunology and Microbiology, hormones, Pseudomonas aeruginosa, lcsh:R, Biofilm, Adhesion, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, peptides, Infectious Diseases, chemistry, Biophysics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
Abstract

International audience; We have previously shown that the C-type Natriuretic Peptide (CNP), a peptide produced by lungs, is able to impact Pseudomonasaeruginosa physiology. In the present work, the effect of CNP at different concentrations on P. aeruginosa biofilm formation was studied and the mechanisms of action of this human hormone on P. aeruginosa were deciphered. CNP was shown to inhibit dynamic biofilm formation in a dose-dependent manner without affecting the bacterial growth at any tested concentrations. The most effective concentrations were 1 and 0.1 µM. At 0.1 µM, the biofilm formation inhibition was fully dependent on the CNP sensor protein AmiC, whereas it was only partially AmiC-dependent at 1 µM, revealing the existence of a second AmiC-independent mode of action of CNP on P. aeruginosa. At 1 µM, CNP reduced both P. aeruginosa adhesion on glass and di-rhamnolipid production and also increased the bacterial membrane fluidity. The various effects of CNP at 1 µM and 0.1 µM on P. aeruginosa shown here should have major consequences to design drugs for biofilm treatment or prevention.

Published
2018
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12. Identification of Components in Frog Skin Secretions with Therapeutic Potential as Antidiabetic Agents

Author

Conlon, J Michael, Moffett, R Charlotte, Leprince, Jérôme, Flatt, Peter, Conlon, J. Michael, Moffett, R. Charlotte, Faculty of Medicine and Health Science, UAE University, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
0301 basic medicine, BRIN-BD11 cells, medicine.medical_treatment, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Incretin, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Frog skin secretions, 03 medical and health sciences, chemistry.chemical_compound, Insulin resistance, In vivo, Lactate dehydrogenase, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], medicine, Glucose homeostasis, Insulin, Edman degradation, Chemistry, Antidiabetic peptide, medicine.disease, 030104 developmental biology, Biochemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Frog Skin
Abstract

International audience; Several peptides that were first identified on the basis of their antimicrobial or immunomodulatory properties have subsequently shown potential for development into agents for the treatment of patients with Type 2 diabetes. A strategy is presented for the isolation and characterization of such peptides in norepinephrine-stimulated skin secretions from a range of frog species. The methodology involves fractionation of the secretions by reversed-phase HPLC, identification of fractions containing components that stimulate the rate of release of insulin from BRIN-BD11 clonal β-cells without simultaneously stimulating the release of lactate dehydrogenase, identification of active peptides in the mass range 1-6 kDa by MALDI-TOF mass spectrometry, purification of the peptides to near homogeneity by further HPLC, and structural characterization by automated Edman degradation. The effect of synthetic replicates of the active peptides on glucose homeostasis in vivo may be evaluated in mice fed a high fat diet to produce obesity, glucose intolerance, and insulin resistance.

Published
2018
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13. GPCR-induced repression of autophagy in glioblastoma cells: impact on lamellipodium expansion and chemotactic migration

Author

Campisi, Daniele, Coly, Pierre-Michaël, Castel, Hélène, Gandolfo, Pierrick, Morin, Fabrice, CASTEL, Hélène, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cancer and Cognition Platform, Ligue Nationale contre le cancer,14000Caen, France, Plateforme Cancer et Cognition, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Cancéropole Nord-Ouest-Ligue Nationale Contre le Cancer (LNCC), Neuroendocrinologie cellulaire et moléculaire, and Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Ligue Nationale Contre le Cancer (LNCC)-Cancéropole Nord-Ouest

Subjects
TheoryofComputation_MISCELLANEOUS, GeneralLiterature_INTRODUCTORYANDSURVEY, [SDV]Life Sciences [q-bio], TheoryofComputation_GENERAL, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV] Life Sciences [q-bio], [SDV.CAN] Life Sciences [q-bio]/Cancer, ComputingMilieux_COMPUTERSANDEDUCATION, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, ComputingMethodologies_GENERAL, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS
Abstract

Price for the best oral presentation; National audience

Published
2018

14. 2-DE Mapping of the Blue Mussel Gill Proteome: The Usual Suspects Revisited

Author

Le Foll, Frank, Rocher, Béatrice, Bultelle, Florence, Chan, Philippe, Foll, Frank, Letendre, Julie, Monsinjon, Tiphaine, Olivier, Stéphanie, Péden, Romain, Poret, Agnès, Vaudry, David, Knigge, Thomas, Stress Environnementaux et BIOsurveillance des milieux aquatiques (SEBIO), Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Institut National de l'Environnement Industriel et des Risques (INERIS), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Sciences Appliquées à L'Environnement (SCALE), Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), LE FOLL, Frank, Institut National de l'Environnement Industriel et des Risques (INERIS)-Université de Reims Champagne-Ardenne (URCA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Normandie Université (NU)-SFR Condorcet, Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS)-Université de Reims Champagne-Ardenne (URCA)-Université de Picardie Jules Verne (UPJV)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-High-tech Research Infrastructures for Life Sciences (HeRacLeS), Normandie Université (NU)-Normandie Université (NU)-Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
animal structures, [SDE.MCG]Environmental Sciences/Global Changes, Clinical Biochemistry, lcsh:QR1-502, Environmental pollution, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Proteomics, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Biochemistry, Article, lcsh:Microbiology, ecotoxicology, chemistry.chemical_compound, [SDV.EE.ECO]Life Sciences [q-bio]/Ecology, environment/Ecosystems, Structural Biology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], post-translational modifications, 14. Life underwater, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Biomarker discovery, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Molecular Biology, ComputingMilieux_MISCELLANEOUS, mass spectrometry, [SDV.TOX.ECO] Life Sciences [q-bio]/Toxicology/Ecotoxicology, biology, Ecology, fungi, proteoforms, 2-DE, biology.organism_classification, Mytilus, bivalve mollusc, environmental stress, Proteasome, chemistry, Proteome, [SDV.TOX.ECO]Life Sciences [q-bio]/Toxicology/Ecotoxicology, Xenobiotic, Blue mussel
Abstract

The Blue Mussel (Mytilus edulis, L. 1758) is an ecologically important and commercially relevant bivalve. Because of its ability to bioconcentrate xenobiotics, it is also a widespread sentinel species for environmental pollution, which has been used in ecotoxicological studies for biomarker assessment. Consequently, numerous proteomics studies have been carried out in various research contexts using mussels of the genus Mytilus, which intended to improve our understanding of complex physiological processes related to reproduction, adaptation to physical stressors or shell formation and for biomarker discovery. Differential-display 2-DE proteomics relies on an extensive knowledge of the proteome with as many proteoforms identified as possible. To this end, extensive characterization of proteins was performed in order to increase our knowledge of the Mytilus gill proteome. On average, 700 spots were detected on 2-DE gels by colloidal blue staining, of which 122 different, non-redundant proteins comprising 203 proteoforms could be identified by tandem mass spectrometry. These proteins could be attributed to four major categories: (i) “metabolism”, including antioxidant defence and degradation of xenobiotics, (ii) “genetic information processing”, comprising transcription and translation as well as folding, sorting, repair and degradation, (iii) “cellular processes”, such as cell motility, transport and catabolism, (iv) “environmental information processing”, including signal transduction and signalling molecules and interaction. The role of cytoskeleton proteins, energetic metabolism, chaperones/stress proteins, protein trafficking and the proteasome are discussed in the light of the exigencies of the intertidal environment, leading to an enhanced stress response, as well as the structural and physiological particularities of the bivalve gill tissue.

Published
2015
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15. Characterization of peptide QRFP (26RFa) and its receptor from amphioxus, Branchiostoma floridae

Author

Ingrid Lundell, Dan Larhammar, Christina Bergqvist, Görel Sundström, Jérôme Leprince, Hubert Vaudry, Bo Xu, Centre Européen de Réalité Virtuelle (CERV), École Nationale d'Ingénieurs de Brest (ENIB), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
MESH: Introns, Lancelet, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Peptide, MESH: Amino Acid Sequence, MESH: Receptors, G-Protein-Coupled, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Base Sequence, MESH: Neuropeptides, Receptors, G-Protein-Coupled, Endocrinology, Branchiostoma floridae, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Cloning, Molecular, MESH: Phylogeny, Receptor, Phylogeny, MESH: Lancelets, Lancelets, chemistry.chemical_classification, biology, MESH: Peptides, Biochemistry, MESH: HEK293 Cells, Intercellular Signaling Peptides and Proteins, Evolution, Molecular Sequence Data, education, Neuropeptide, Transfection, Animals, Humans, MESH: Cloning, Molecular, G protein-coupled receptor, Amino Acid Sequence, Amphioxus, MESH: Humans, MESH: Molecular Sequence Data, Base Sequence, Human evolutionary genetics, MESH: Transfection, Neuropeptides, QRFP, biology.organism_classification, Introns, HEK293 Cells, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Animal Science and Zoology, Peptides
Abstract

International audience; A peptide ending with RFamide (Arg-Phe-amide) was discovered independently by three different laboratories in 2003 and named 26RFa or QRFP. In mammals, a longer version of the peptide, 43 amino acids, was identified and found to bind to the orphan G protein-coupled receptor GPR103. We searched the genome database of Branchiostoma floridae (Bfl) for receptor sequences related to those that bind peptides ending with RFa or RYa (including receptors for NPFF, PRLH, GnIH, and NPY). One receptor clustered in phylogenetic analyses with mammalian QRFP receptors. The gene has 3 introns in Bfl and 5 in human, but all intron positions differ, implying that the introns were inserted independently. A QRFP-like peptide consisting of 25 amino acids and ending with RFa was identified in the amphioxus genome. Eight of the ten last amino acids are identical between Bfl and human. The prepro-QRFP gene in Bfl has one intron in the propeptide whereas the human gene lacks introns. The Bfl QRFP peptide was synthesized and the receptor was functionally expressed in human cells. The response was measured as inositol phosphate (IP) turnover. The Bfl QRFP peptide was found to potently stimulate the receptor's ability to induce IP turnover with an EC50 of 0.28nM. Also the human QRFP peptides with 26 and 43 amino acids were found to stimulate the receptor (1.9 and 5.1nM, respectively). Human QRFP with 26 amino acids without the carboxyterminal amide had dramatically lower potency at 1.3μM. Thus, we have identified an amphioxus QRFP-related peptide and a corresponding receptor and shown that they interact to give a functional response.

Published
2015
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16. THE CONCISE GUIDE TO PHARMACOLOGY 2017/18: Overview

Author

Alexander, Stephen PH, Kelly, Eamonn, Marrion, Neil, Peters, John, Faccenda, Elena, Harding, Simon, Pawson, Adam, Sharman, Joanna, Southan, Christopher, Buneman, O Peter, Cidlowski, John, Christopoulos, Arthur, Davenport, Anthony, Fabbro, Doriano, Spedding, Michael, Striessnig, Jörg, Davies, Jamie, Abbracchio, M P, Leprince, Jérôme, Montana State University (MSU), National Institutes of Environmental Health Sciences, National Institutes of Health [Bethesda] (NIH), Experimental Medicine and Immunotherapeutics [Cambridge, UK], University of Cambridge [UK] (CAM), Novartis Pharma AG, Neuroscience et Pharmacologie, Institut de Recherches Servier, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
MESH: Humans, MESH: Knowledge Bases, Databases, Pharmaceutical, Knowledge Bases, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, The Concise Guide to Pharmacology 2017/18, Proteins, MESH: Databases, Pharmaceutical, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Ligands, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Humans, MESH: Proteins
Abstract

International audience; The Concise Guide to PHARMACOLOGY 2017/18 is the third in this series of biennial publications. This version provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to an open access knowledgebase of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.13882/full. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are eight areas of focus: G protein-coupled receptors, ligand-gated ion channels, voltage-gated ion channels, other ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2017, and supersedes data presented in the 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature Committee of the Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Published
2017
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17. The Arg-Phe-amide peptide 26RFa/glutamine RF-amide peptide and its receptor: IUPHAR Review 24

Author

Leprince, Jérôme, Bagnol, Didier, Bureau, Ronan, Fukusumi, Shoji, Granata, Riccarda, Hinuma, Shuji, Larhammar, Dan, Primeaux, Stefany, Sopkova‐de Oliveiras Santos, Jana, Tsutsui, Kazuyoshi, Ukena, Kazuyoshi, Vaudry, Hubert, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), ARENA Pharmaceuticals, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Université de Tsukuba = University of Tsukuba, Università degli studi di Torino (UNITO), Osaka University [Osaka], Uppsala University, Louisiana State University (LSU), Waseda University, and Hiroshima University

Subjects
Receptors, Neuropeptide, MESH: Humans, MESH: Peptides, MESH: Receptors, Neuropeptide, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neuropeptides, IUPHAR Review, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Animals, Humans, Intercellular Signaling Peptides and Proteins, MESH: Animals, Peptides
Abstract

International audience; The RFamide neuropeptide 26RFa was first isolated from the brain of the European green frog on the basis of cross-reactivity with antibodies raised against bovine neuropeptide FF (NPFF). 26RFa and its N-terminally extended form glutamine RF-amide peptide (QRFP) have been identified as cognate ligands of the former orphan receptor GPR103, now renamed glutamine RF-amide peptide receptor (QRFP receptor). The 26RFa/QRFP precursor has been characterized in various mammalian and non-mammalian species. In the brain of mammals, including humans, 26RFa/QRFP mRNA is almost exclusively expressed in hypothalamic nuclei. The 26RFa/QRFP transcript is also present in various organs especially in endocrine glands. While humans express only one QRFP receptor, two isoforms are present in rodents. The QRFP receptor genes are widely expressed in the CNS and in peripheral tissues, notably in bone, heart, kidney, pancreas and testis. Structure-activity relationship studies have led to the identification of low MW peptidergic agonists and antagonists of QRFP receptor. Concurrently, several selective non-peptidic antagonists have been designed from high-throughput screening hit optimization. Consistent with the widespread distribution of QRFP receptor mRNA and 26RFa binding sites, 26RFa/QRFP exerts a large range of biological activities, notably in the control of energy homeostasis, bone formation and nociception that are mediated by QRFP receptor or NPFF2. The present report reviews the current knowledge concerning the 26RFa/QRFP-QRFP receptor system and discusses the potential use of selective QRFP receptor ligands for therapeutic applications.

Published
2017
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18. Cytotoxic peptides with insulin-releasing activities from skin secretions of the Italian stream frog Rana italica (Ranidae)

Author

Conlon, J Michael, Musale, Vishal, Attoub, Samir, Mangoni, Maria Luisa, Leprince, Jérôme, Coquet, Laurent, Jouenne, Thierry, Abdel-Wahab, Yasser, Flatt, Peter, Rinaldi, Andrea, Conlon, J. Michael, Faculty of Medicine and Health Science, UAE University, Department of Biochemical Sciences 'Rossi Fanelli', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Polymères, biopolymères, membranes (PBM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)

Subjects
frog skin, antimicrobial peptide, cytotoxicity, ranidae, insulin relase, Ranidae, MESH: Staphylococcus epidermidis, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: HT29 Cells, MESH: Anura, Microbial Sensitivity Tests, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Hemolysis, Amphibian Proteins, Mice, MESH: Skin, MESH: Amphibian Proteins, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Escherichia coli, Staphylococcus epidermidis, Animals, Humans, insulin release, MESH: Animals, MESH: Mice, Skin, MESH: Microbial Sensitivity Tests, MESH: Humans, MESH: Ranidae, MESH: Escherichia coli, MESH: Antimicrobial Cationic Peptides, MESH: Hemolysis, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Anura, HT29 Cells, Antimicrobial Cationic Peptides
Abstract

International audience; Peptidomic analysis of norepinephrine-stimulated skin secretions from Italian stream frog Rana italica led to the purification and characterization of two host-defense peptides differing by a single amino acid residue belonging to the brevinin-1 family (brevinin-1ITa and -1ITb), a peptide belonging to the temporin family (temporin-ITa) and a component identified as prokineticin Bv8. The secretions contained relatively high concentrations of the methionine-sulphoxide forms of brevinin-1ITa and -1ITb suggesting that these peptides may have a role as antioxidants in the skin of this montane frog. Brevinin-1ITa (IVPFLLGMVPKLVCLITKKC) displayed potent cytotoxicity against non-small cell lung adenocarcinoma A549 cells (LC50 = 18 μM), breast adenocarcinoma MDA-MB-231 cells (LC50 = 8 μM) and colorectal adenocarcinoma HT-29 cells (LC50 = 18 μM), but the peptide was also strongly hemolytic against mouse erythrocytes (LC50 = 7 μM). Temporin-ITa (VFLGAIAQALTSLLGKL.NH2 ) was between three and fivefold less potent against these cells. Brevinin-1ITa inhibited growth of both Gram-positive Staphylococcus epidermidis and Gram-negative Escherichia coli as well as a strain of the opportunist yeast pathogen Candida parapsilosis, whereas temporin-ITa was active only against S. epidermidis and C. parapsilosis. Both peptides stimulated the release of insulin from BRIN-BD11 clonal β-cells at concentrations ≥1 nM, but brevinin-1ITa was cytotoxic to the cells at concentrations ≥3 μM. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd.

Published
2017
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19. Investigations of octylglyceryl dextran- graft -poly(lactic acid) nanoparticles for peptide delivery to the brain

Author

Boussahel, Asme, Ibegbu, Daniel, Lamtahri, Rhita, Maucotel, Julie, Chuquet, Julien, Lefranc, Benjamin, Leprince, Jérôme, Roldo, Marta, Mével, Jean-Claude Le, Gorecki, Darek, Barbu, Eugen, Chuquet, Julie, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), Neuroendocrinologie cellulaire et moléculaire, Laboratoire d'Informatique, de Traitement de l'Information et des Systèmes (LITIS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), and Normandie Université (NU)

Subjects
0301 basic medicine, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Medicine (miscellaneous), Peptide, 02 engineering and technology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Blood-Brain Barrier, Mice, chemistry.chemical_compound, Drug Delivery Systems, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], General Materials Science, MESH: Animals, MESH: Dextrans, Cytotoxicity, chemistry.chemical_classification, MESH: Peptides, Dextrans, 021001 nanoscience & nanotechnology, MESH: Polyesters, Lactic acid, Dextran, Biochemistry, Blood-Brain Barrier, dextran, Drug delivery, 0210 nano-technology, Materials science, Polyesters, brain, education, MESH: Drug Delivery Systems, Biomedical Engineering, Neuropeptide, Bioengineering, Development, Cell Line, 03 medical and health sciences, MESH: Brain, In vivo, Animals, Humans, MESH: Particle Size, Particle Size, MESH: Mice, MESH: Humans, neuropeptides, Biomedical Sciences, Angiotensin II, MESH: Cell Line, 030104 developmental biology, chemistry, drug delivery, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, nanoparticles, Peptides, MESH: Nanoparticles
Abstract

Aim - Develop modified dextran nanoparticles showing potential to assist with drug permeation across the blood–brain barrier for the delivery of neuropeptides.Methods - Nanoparticles loaded by emulsification with model macromolecular actives were characterized in terms of stability, cytotoxicity and drug-release behavior. Peptide-loaded nanoformulations were tested in an in vivo trout model and in food-deprived mice. Results - Nanoformulations loaded with model peptides showed good stability and appeared nontoxic in low concentration against human brain endothelial cells. They were found to preserve the bioactivity of loaded peptides (angiotensin II) as demonstrated in vivo using a trout model, and to induce a transient reduction of food consumption in mice when loaded with an anorexigenic octaneuropeptide. Conclusion - Octylglyceryl dextran-graft-poly(lactic acid) nanoparticles formulated by emulsification demonstrate potential for peptide delivery.

Published
2017
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20. Long-Term Control of Hypercortisolism by Vandetanib in a Case of Medullary Thyroid Carcinoma with a Somatic RET Mutation

Author

Marie Bienvenu-Perrard, Anne-Cécile Paepegaey, Najiba Lahlou, Lionel Groussin, Estelle Louiset, Léopoldine Bricaire, Béatrix Cochand-Priollet, Marco Alifano, Nelly Burnichon, Pierre-Olivier Sarfati, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, Oncology, Hydrocortisone, MESH: Carcinoma, Neuroendocrine, Somatic cell, Endocrinology, Diabetes and Metabolism, Cushing's syndrome, Vandetanib, MESH: Cushing Syndrome, 0302 clinical medicine, Endocrinology, Piperidines, medullary thyroid carcinoma, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Protein Kinase Inhibitors, Cushing Syndrome, MESH: Middle Aged, Cytoreduction Surgical Procedures, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Debulking, MESH: Hydrocortisone, 3. Good health, MESH: Quinazolines, MESH: Piperidines, MESH: Thyroid Neoplasms, 030220 oncology & carcinogenesis, Thyroidectomy, Neck Dissection, Tyrosine kinase, Long term control, medicine.drug, Calcitonin, medicine.medical_specialty, vandetanib, Medullary cavity, 030209 endocrinology & metabolism, MESH: Proto-Oncogene Proteins c-ret, MESH: Thyroidectomy, Thyroid carcinoma, 03 medical and health sciences, Internal medicine, MESH: Neck Dissection, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Humans, MESH: Cytoreduction Surgical Procedures, Thyroid Neoplasms, Protein Kinase Inhibitors, MESH: Humans, hypercortisolism, MESH: Calcitonin, business.industry, Proto-Oncogene Proteins c-ret, MESH: Male, Carcinoma, Neuroendocrine, Quinazolines, business, RET
Abstract

Medullary thyroid carcinomas (MTCs) complicated by ectopic Cushing's syndrome (CS) have a poor prognosis, partially due to the difficulty in controlling hypercortisolism by adrenal blocking drugs. Recent reports (including the initial follow-up of this patient) have suggested that tyrosine kinase inhibitors (TKIs) may be a therapeutic option due to an anti-secretory action on ACTH. However, there is a lack of long-term follow-up studies.The case is reported of a 58-year-old man with MTC-related CS resistant to a combination of several anti-cortisolic drugs. Vandetanib, an oral multi-TKI that targets RET in particular, was initiated, and a rapid reversal of the hypercortisolism was observed without any change in tumor size. Vandetanib was briefly interrupted twice, once for 45 days because of side effects and a second time for 10 days to schedule surgical debulking. Each time, plasma cortisol and calcitonin levels increased after TKI withdrawal and were rapidly lowered by vandetanib reintroduction. As described in other cases of CS caused by MTC, a marked ACTH increase after desmopressin stimulation was observed before vandetanib therapy. In contrast, a blunted ACTH response to desmopressin was documented throughout the course of vandetanib treatment. This modulation of the tumoral ACTH production is a strong argument in favor of a TKI anti-secretory action. A left thyroid lobectomy and a modified neck dissection were performed one year after the initiation of vandetanib in order to reduce the tumor mass. An activating M918T RET (c.2753TC) somatic mutation was identified in a lymph node metastasis.Three years and eight months after vandetanib initiation, there was no sign of recurrence of hypercortisolism. This case illustrates the long-term effectiveness of vandetanib in maintaining the control of hypercortisolism in MTC-related CS.

Published
2017
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21. Glioprotective effect of Ulva rigida extract against UVB cellular damages

Author

Mohamed Amri, Olfa Masmoudi, Ines Bourguiba, Annick Schaumann, Amine Ben Mlouka, Julie Hardouin, Thierry Jouenne, Amel Zehlila, Pascal Cosette, Polymères Biopolymères Surfaces (PBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut de Chimie du CNRS (INC)-Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plate-forme de Protéomique PISSARO, Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), Université de Tunis El Manar (UTM), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, biology, Calmodulin, [SDV]Life Sciences [q-bio], Proteolytic enzymes, biology.organism_classification, Cellular viability, Ulva rigida, Lipid peroxidation, Superoxide dismutase, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Biochemistry, Algae, chemistry, Catalase, biology.protein, Agronomy and Crop Science, 030217 neurology & neurosurgery, ComputingMilieux_MISCELLANEOUS
Abstract

Natural molecules from different origins exhibit high therapeutic potential. Among them, molecules from marine algae are of particular interest. In the present study, we investigated the preventive effect of a protein extract (PE) of Ulva rigida against UVB-induced cellular damages. We demonstrated that a treatment of cortical astrocytes with 50 μg of PE induced a strong glioprotective effect and suppressed harmful effects of UVB radiations, increasing in particular cellular viability. In additional assays, this extract promoted the activity of catalase and superoxide dismutase and inhibited the production of stress markers, such as H 2 O 2 or lipid peroxidation. As expected, proteolytic digestion or heating treatment of algal extract inhibited this preventive effect, arguing for the predominant role of the protein fraction. Thereafter, proteomic investigations allowed to identify several proteins from the extract, among which calmodulin revealed to represent an important contributor to the observed protective activities.

Published
2017
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22. A potential role for the secretogranin II-derived peptide EM66 in the hypothalamic regulation of feeding behaviour

Author

Nicolas Chartrel, Youssef Anouar, Julie Maucotel, Jérôme Leprince, Loubna Boukhzar, F. Trebak, Gaëtan Prévost, A. Alaoui, Saloua Cherifi, Céline Duparc, Marie Christine Picot, Arnaud Arabo, Rabia Magoul, Isabelle Dubuc, Neuropsycho-pharmacologie expérimentale, Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), UFR des Sciences et Techniques Mont-Saint-Aignan, University of Bern, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroscience Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie cellulaire et moléculaire, Les Hôptaux universitaires de Strasbourg (HUS), CHU Strasbourg, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), and Centre National d'Études Spatiales [Toulouse] (CNES)

Subjects
0301 basic medicine, Male, Endocrinology, Diabetes and Metabolism, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Mice, 0302 clinical medicine, Endocrinology, Gene expression, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Receptor, MESH: Peptide Fragments, ComputingMilieux_MISCELLANEOUS, biology, Chemistry, digestive, oral, and skin physiology, Granin, Neuropeptide Y receptor, high-fat diet, Infusions, Intraventricular, Hypothalamus, Secretogranin II, MESH: Feeding Behavior, MESH: Infusions, Intraventricular, hormones, hormone substitutes, and hormone antagonists, medicine.medical_specialty, endocrine system, neuropeptide Y, EM66, Neuropeptide, 030209 endocrinology & metabolism, 03 medical and health sciences, Cellular and Molecular Neuroscience, Food Preferences, feeding behaviour, Proopiomelanocortin, Arcuate nucleus, MESH: Mice, Inbred C57BL, Internal medicine, medicine, pro-opiomelanocortin, Animals, MESH: Food Preferences, neuropeptide, MESH: Mice, Caloric Restriction, MESH: Caloric Restriction, Endocrine and Autonomic Systems, Appetite Regulation, Feeding Behavior, MESH: Hypothalamus, MESH: Male, Peptide Fragments, Mice, Inbred C57BL, 030104 developmental biology, nervous system, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Secretogranin II, MESH: Appetite Regulation
Abstract

International audience; EM66 is a conserved 66-amino acid peptide derived from secretogranin II (SgII), a member of the granin protein family. EM66 is widely distributed in secretory granules of endocrine and neuroendocrine cells, as well as in hypothalamic neurones. Although EM66 is abundant in the hypothalamus, its physiological function remains to be determined. The present study aimed to investigate a possible involvement of EM66 in the hypothalamic regulation of feeding behaviour. We show that i.c.v. administration of EM66 induces a drastic dose-dependent inhibition of food intake in mice deprived of food for 18 hours, which is associated with an increase of hypothalamic pro-opiomelanocortin (POMC) and melanocortin-3 receptor mRNA levels and c-Fos immunoreactivity in the POMC neurones of the arcuate nucleus. By contrast, i.c.v. injection of EM66 does not alter the hypothalamic expression of neuropeptide Y (NPY), or that of its Y1 and Y5 receptors. A 3-month high-fat diet (HFD) leads to an important decrease of POMC and SgII mRNA levels in the hypothalamus, whereas NPY gene expression is not affected. Finally, we show that a 48 hours of fasting in HFD mice decreases the expression of POMC and SgII mRNA, which is not observed in mice fed a standard chow. Taken together, the present findings support the view that EM66 is a novel anorexigenic neuropeptide regulating hypothalamic feeding behaviour, at least in part, by activating the POMC neurones of the arcuate nucleus.

Published
2017
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23. Host-defense peptides from skin secretions of Fraser's clawed frog Xenopus fraseri (Pipidae): Further insight into the evolutionary history of the Xenopodinae

Author

Jolanta Kolodziejek, Jérôme Leprince, Milena Mechkarska, Laurent Coquet, Thierry Jouenne, Norbert Nowotny, J. Michael Conlon, Hubert Vaudry, Faculty of Medicine and Health Science, UAE University, Zoonoses and Emerging Infections Group, Polymères, biopolymères, membranes (PBM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Xenopus, Pipidae, MESH: Amino Acid Sequence, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Xenopus Proteins, Biochemistry, chemistry.chemical_compound, Magainin, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, MESH: Xenopus, MESH: Xenopus Proteins, Skin, Silurana, Genetics, 0303 health sciences, Xenopus fraseri, PGLa, biology, MESH: Peptides, MESH: Antimicrobial Cationic Peptides, Xenopus andrei, Host-defense peptide, Molecular Sequence Data, Magainins, Xenopus pygmaeus, MESH: Magainins, Frog skin, 03 medical and health sciences, MESH: Skin, Animals, Amino Acid Sequence, Molecular Biology, 030304 developmental biology, MESH: Molecular Sequence Data, Xenopus amieti, biology.organism_classification, Molecular biology, Caerulein-precursor fragment, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Peptides, 030217 neurology & neurosurgery, Antimicrobial Cationic Peptides
Abstract

International audience; Peptidomic analysis of norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus fraseri Boulenger, 1905 (Pipidae) led to identification of 13 host-defense peptides. The primary structures of the peptides demonstrate that they belong to the magainin (3 peptides), peptide glycine-leucine-amide, PGLa (4 peptides), and xenopsin-precursor fragment, XPF (2 peptides) families, first identified in Xenopus laevis, together with caerulein precursor fragment-related peptides, CPF-RP (4 peptides), first identified in Silurana tropicalis. In addition, the secretions contain a molecular variant of xenopsin displaying the substitution Arg(4)→Lys compared with X. laevis xenopsin and peptide glycine-tyrosine-amide (PGYa) (GRIIPIYPEFERVFA KKVYPLY.NH2) whose function is unknown. The most potent antimicrobial peptide identified is CPF-RP-F1 (GFGSVLGKALKFGANLL.NH2) with MIC=12.5μM against Staphylococcus aureus and 50μM against Escherichia coli. On the basis of similarities in morphology and advertisement calls, X. fraseri has been placed in a species group that includes the octoploids Xenopus amieti and Xenopus andrei, and the tetraploid Xenopus pygmaeus. Cladistic analyses based upon the primary structures of magainin, PGLa, and CPF-RP peptides support a close evolutionary relationship between X. fraseri, X. amieti and X. andrei but suggest a more distant relationship with X. pygmaeus.

Published
2014
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24. MOLECULAR EVOLUTION OF GPCRS: 26Rfa/GPR103

Author

Kazuyoshi Tsutsui, Hubert Vaudry, Kazuyoshi Ukena, Jérôme Leprince, Tomohiro Osugi, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
26RFa/QRFP, food intake, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Blood Pressure, MESH: Amino Acid Sequence, MESH: Receptors, G-Protein-Coupled, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, MESH: Eating, Energy homeostasis, Nociceptive Pain, Receptors, G-Protein-Coupled, Eating, MESH: Bone Development, Endocrinology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, hypothalamus, MESH: Nociceptive Pain, Receptor, MESH: Evolution, Molecular, MESH: Energy Metabolism, Intracellular Signaling Peptides and Proteins, MESH: Blood Pressure, Cell biology, Hypothalamus, medicine.drug, medicine.medical_specialty, MESH: Orexins, Molecular Sequence Data, MESH: Sequence Alignment, Neuropeptide, Biology, Evolution, Molecular, Molecular evolution, MESH: Intracellular Signaling Peptides and Proteins, Internal medicine, Orexigenic, medicine, Animals, Humans, Amino Acid Sequence, G protein-coupled receptor, neuropeptide, Molecular Biology, Orexins, Bone Development, MESH: Molecular Sequence Data, MESH: Humans, Neuropeptides, QRFP, MESH: Hypothalamus, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Energy Metabolism, Sequence Alignment
Abstract

Neuropeptides possessing the Arg-Phe-NH2 (RFamide) motif at their C-termini (designated as RFamide peptides) have been characterized in a variety of animals. Among these, neuropeptide 26RFa (also termed QRFP) is the latest member of the RFamide peptide family to be discovered in the hypothalamus of vertebrates. The neuropeptide 26RFa/QRFP is a 26-amino acid residue peptide that was originally identified in the frog brain. It has been shown to exert orexigenic activity in mammals and to be a ligand for the previously identified orphan G protein-coupled receptor, GPR103 (QRFPR). The cDNAs encoding 26RFa/QRFP and QRFPR have now been characterized in representative species of mammals, birds, and fish. Functional studies have shown that, in mammals, the 26RFa/QRFP–QRFPR system may regulate various functions, including food intake, energy homeostasis, bone formation, pituitary hormone secretion, steroidogenesis, nociceptive transmission, and blood pressure. Several biological actions have also been reported in birds and fish. This review summarizes the current state of identification, localization, and understanding of the functions of 26RFaQRFP and its cognate receptor, QRFPR, in vertebrates.

Published
2014
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25. Does Somatostatin Have a Role in the Regulation of Cortisol Secretion in Primary Pigmented Nodular Adrenocortical Disease (PPNAD)? A Clinical and in Vitro Investigation

Author

Leo J. Hofland, Meg Keil, Constantine A. Stratakis, M Nesterova, Paraskevi Xekouki, Dimitrios Avgeropoulos, Hervé Lefebvre, Rabia Cherqaoui, Ninet Sinaii, Zakariae Bram, Estelle Louiset, Christoforos Giatzakis, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Section on Endocrinology and Genetics, National Institutes of Health (NIH)-National Institute of Child Health and Human Development, and Internal Medicine

Subjects
Male, Pathology, Hydrocortisone, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Octreotide, Biochemistry, Endocrinology, MESH: Child, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Single-Blind Method, Receptors, Somatostatin, Child, Cross-Over Studies, MESH: Middle Aged, JCEM Online: Advances in Genetics, Adrenal cortex, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Infant, MESH: Hydrocortisone, 3. Good health, medicine.anatomical_structure, Somatostatin, Child, Preschool, Immunohistochemistry, Female, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Adrenal Cortex Diseases, Adult, Cortisol secretion, endocrine system, medicine.medical_specialty, Adolescent, education, Context (language use), MESH: Cross-Over Studies, Cell Line, Internal medicine, MESH: Receptors, Somatostatin, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Humans, MESH: Adolescent, MESH: Humans, MESH: Octreotide, business.industry, MESH: Adrenal Cortex Diseases, MESH: Child, Preschool, Biochemistry (medical), Infant, MESH: Adult, MESH: Single-Blind Method, MESH: Male, MESH: Cell Line, Adrenal Cortex, MESH: Adrenal Cortex, MESH: Pigmentation Disorders, business, Pigmentation Disorders, MESH: Female, Primary pigmented nodular adrenocortical disease
Abstract

Context: Somatostatin (SST) receptors (SSTRs) are expressed in a number of tissues, including the adrenal cortex, but their role in cortisol secretion has not been well characterized. Objectives: The objective of the study was to investigate the expression of SSTRs in the adrenal cortex and cultured adrenocortical cells from primary pigmented nodular adrenocortical disease (PPNAD) tissues and to test the effect of a single injection of 100 mu g of the SST analog octreotide on cortisol secretion in patients with PPNAD. Setting and Design: The study was conducted at an academic research laboratory and clinical research center. Expression of SSTRs was examined in 26 PPNAD tissues and the immortalized PPNAD cell line CAR47. Ten subjects with PPNAD underwent a randomized, single-blind, crossover study of their cortisol secretion every 30 minutes over 12 hours (6:00 PM to 6:00 AM) before and after the midnight administration of octreotide 100 mu g sc. Methods: SSTRs expression was investigated by quantitative PCR and immunohistochemistry. The CAR47 and primary cell lines were studied in vitro. The data of the 10 patients were analyzed before and after the administration of octreotide. Results: All SSTRs, especially SSTR1-3, were expressed in PPNAD at significantly higher levels than in normal adrenal. SST was found to differentially regulate expression of its own receptors in the CAR47 cell line. However, the administration of octreotide to patients with PPNAD did not significantly affect cortisol secretion. Conclusions: SSTRs are overexpressed in PPNAD tissues in comparison with normal adrenal cortex. Octreotide did not exert any significant effect on cortisol secretion in a short clinical pilot study in a small number of patients with PPNAD, but long-acting SST analogs targeting multiple SSTRs may be worth investigating in this condition.

Published
2014
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26. MECHANISMS IN ENDOCRINOLOGY: Autocrine/paracrine regulatory mechanisms in adrenocortical neoplasms responsible for primary adrenal hypercorticism

Author

Estelle Louiset, Gaëtan Prévost, Hervé Lefebvre, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Rouen, Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Adrenal disorder, Endocrinology, Diabetes and Metabolism, Local hormone, 030209 endocrinology & metabolism, Adrenal neoplasm, MESH: Adrenal Cortex Neoplasms, Biology, MESH: Adrenocortical Hyperfunction, MESH: Adrenal Cortex Hormones, 03 medical and health sciences, Paracrine signalling, 0302 clinical medicine, Endocrinology, MESH: Renin-Angiotensin System, Internal medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, MESH: Paracrine Communication, MESH: Adrenal Glands, Autocrine signalling, 030304 developmental biology, 0303 health sciences, MESH: Humans, Adrenal gland, General Medicine, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, medicine.disease, Hyperaldosteronism, Angiotensin II, medicine.anatomical_structure, MESH: Autocrine Communication
Abstract

International audience; A wide variety of autocrine/paracrine bioactive signals are able to modulate corticosteroid secretion in the human adrenal gland. These regulatory factors, released in the vicinity of adrenocortical cells by diverse cell types comprising chromaffin cells, nerve terminals, cells of the immune system, endothelial cells, and adipocytes, include neuropeptides, biogenic amines, and cytokines. A growing body of evidence now suggests that paracrine mechanisms may also play an important role in the physiopathology of adrenocortical hyperplasias and tumors responsible for primary adrenal steroid excess. These intra-adrenal regulatory systems, although globally involving the same actors as those observed in the normal gland, display alterations at different levels, which reinforce the capacity of paracrine factors to stimulate the activity of adrenocortical cells. The main modifications in the adrenal local control systems reported by now include hyperplasia of cells producing the paracrine factors and abnormal expression of the latter and their receptors. Because steroid-secreting adrenal neoplasms are independent of the classical endocrine regulatory factors angiotensin II and ACTH, which are respectively suppressed by hyperaldosteronism and hypercortisolism, these lesions have long been considered as autonomous tissues. However, the presence of stimulatory substances within the neoplastic tissues suggests that steroid hypersecretion is driven by autocrine/paracrine loops that should be regarded as promising targets for pharmacological treatments of primary adrenal disorders. This new potential therapeutic approach may constitute an alternative to surgical removal of the lesions that is classically recommended in order to cure steroid excess.

Published
2013
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27. Effect of Carbidopa on 18 F-FDOPA Uptake in Insulinoma: From Cell Culture to Small-Animal PET Imaging

Author

Boisson, Frederic, Detour, Julien, Pierre, Alice, Boisson, Frédéric, Kreutter, Guillaume, Lavaux, Thomas, Namer, Izzie Jacques, Kessler, Laurence, Brasse, David, Marchand, Patrice, Imperiale, Alessio, Institut Pluridisciplinaire Hubert Curien (IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Radiobiologie, Hadronthérapie et Imagerie Moléculaire (DRHIM-IPHC), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Stress vasculaire et tissulaire en transplantation : microparticules et environnement, Université de Strasbourg (UNISTRA), Laboratoire de Biochimie et de Biologie Moléculaire, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], Service de Biophysique et Médecine Nucléaire, CHU Strasbourg-Université Louis Pasteur - Strasbourg I-Hôpital de Hautepierre [Strasbourg], CHU Strasbourg, Laboratoire de neurosciences cognitives et adaptatives (LNCA), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Fédération de médecine translationnelle, École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Service de Diabetologie Université de Strasbourg, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centre de biophysique moléculaire (CBM), Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)

Subjects
endocrine system, medicine.medical_specialty, Metabolic Clearance Rate, Mice, Nude, Pharmacology, 18F-FDOPA, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, Subcutaneous injection, 0302 clinical medicine, In vivo, Internal medicine, Cell Line, Tumor, medicine, Animals, Radiology, Nuclear Medicine and imaging, Tissue Distribution, small animal PET, RIN-m5F, Insulinoma, ComputingMilieux_MISCELLANEOUS, [PHYS]Physics [physics], medicine.diagnostic_test, Chemistry, Carbidopa, Reproducibility of Results, medicine.disease, Image Enhancement, In vitro, 3. Good health, Dihydroxyphenylalanine, Pancreatic Neoplasms, PET, Endocrinology, Positron emission tomography, Cell culture, Organ Specificity, 030220 oncology & carcinogenesis, Positron-Emission Tomography, [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], Female, Beta cell, Radiopharmaceuticals, medicine.drug
Abstract

International audience; Patient premedication with carbidopa seems to improve the accuracy of 6-F-18-fluoro-3,4-dihydroxy-L-phenylalanine (F-18-FDOPA) PET for insulinoma diagnosis. However, the risk of PET false-negative results in the presence of carbidopa is a concern. Consequently, we aimed to evaluate the effect of carbidopa on F-18-FDOPA uptake in insulinoma beta-cells and an insulinoma xenograft model in mice. Methods: F-18-FDOPA in vitro accumulation was assessed in the murine beta-cell line RIN-m5F. In vivo small-animal PET experiments were performed on tumor-bearing nude mice after subcutaneous injection of RIN-m5F cells. Experiments were conducted with and without carbidopa pretreatment. Results: Incubation of RIN-m5F cells with 80 mu M carbidopa did not significantly affect the cellular accumulation of F-18-FDOPA. Tumor xenografts were clearly detectable by small-animal PET in all cases. Insulinoma xenografts in carbidopa-treated mice showed significantly higher F-18-FDOPA uptake than those in nontreated mice. Regardless of carbidopa premedication, the xenografts were characterized by an early increase in F-18-FDOPA uptake and then a progressive reduction over time. Conclusion: Carbidopa did not influence in vitro F-18-FDOPA accumulation in RIN-m5F cells but improved insulinoma imaging in vivo. Our findings increase current knowledge about the F-18-FDOPA uptake profile of RIN-m5F cells and a related xenograft model. To our knowledge, the present work represents the first pre clinical research specifically focused on insulinomas, with potential translational implications.

Published
2017
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28. Effect of human QRFPR ligands in the insulin tolerance test in mice

Author

Alim, Karima, Lefranc, Benjamin, Picot, Marie, Prévost, Gaëtan, Chuquet, Julien, Vaudry, David, Vaudry, Hubert, Chartrel, Nicolas, Leprince, Jérôme, Leprince, Jérôme, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), and Neuroendocrinologie cellulaire et moléculaire

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [CHIM.THER] Chemical Sciences/Medicinal Chemistry, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, [SDV.BC.IC] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2017

29. Characterization of fluorescent synthetic epicocconone-based dye through advanced light microscopies for live cell imaging applications

Author

Alexis Lebon, Stéphane Leleu, Ludovic Galas, Xavier Franck, Agathe Boulangé, Magalie Bénard, Thibault Gallavardin, Caroline Perraudeau, Damien Schapman, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Unité de Néonatalogie [Hôpital des enfants Toulouse], Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Lab Phys Collis Electron & Atom, Université de Brest (UBO), Neuroendocrinologie cellulaire et moléculaire, Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Dye, General Chemical Engineering, Analytical chemistry, Epicocconone, Organic synthesis, 02 engineering and technology, Fluorophore, 010402 general chemistry, 01 natural sciences, law.invention, Live cell imaging, Confocal microscopy, law, Microscopy, Organelle, [CHIM]Chemical Sciences, Cellular biology, Chemistry, Process Chemistry and Technology, Advanced light microscopies, 021001 nanoscience & nanotechnology, Fluorescence, 0104 chemical sciences, Membrane, Covalent bond, Biophysics, 0210 nano-technology
Abstract

International audience; Identification of new fluorescent biomarkers is a key issue to decipher mechanisms in living cells. Isolated from the fungus Epicoccum nigrum, natural epicocconone (NE) establishes a covalent and reversible link with primary amines and has been identified as a new fluorescent dye for cell imaging. In the present study, the properties of a synthetic and multifunctional analogue of epicocconone (SE) have been compared to those of NE through 1-photon (1P) and 2-photon (2P) advanced light microscopies. 1P Λλ confocal microscopy analyses revealed that, in cell culture medium, SE and NE displayed two peaks of excitation (ex) at 480 and 530 nm and a large band of emission (em) with a maximum at 610 nm. In living cells, SE presented sharper bands compared to NE with maxima at 545 nm (ex) and 605 nm (em). In 2P microscopy, SE and NE presented maxima around 790 nm (ex) and 595 nm (em) when diluted in cell culture medium. In living cells, SE did not present any large disturbing blue-shift for emission that was observed for NE. In addition, 2P bands for SE were sharper than the NE ones. SE was 2–3 times more fluorescent than NE as determined through 1P and 2P approaches. SE did not induce any cytotoxicity and was adapted for time-lapse acquisition. In PC12 cells, SE broadly labeled nuclear and plasma membranes, vesicles-like structures and organelles including the Golgi apparatus and mitochondria. Taken together, these data indicate that SE has appropriate properties for in vitro and in vivo cell biology studies and presents many advantages compared to NE for 1P and 2P microscopies.

Published
2017
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30. Effect of food deprivation on the hypothalamic gene expression of the secretogranin II-derived peptide EM66 in rat

Author

Nicolas Chartrel, Marie Christine Picot, Fatima Trebak, Rabia Magoul, A. Alaoui, Gaëtan Prévost, Jérôme Leprince, Youssef Anouar, Isabelle Dubuc, Neuropsycho-pharmacologie expérimentale, Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Sidi Mohamed Ben Abdellah (USMBA), Neuroendocrinologie cellulaire et moléculaire, and Sidi Mohammed Ben Abdellah University

Subjects
Male, 0301 basic medicine, Pro-Opiomelanocortin, Time Factors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Gene Expression, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 0302 clinical medicine, Gene expression, MESH: Behavior, Animal, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Pro-Opiomelanocortin, Neuropeptide Y, MESH: Animals, MESH: Peptide Fragments, 2. Zero hunger, chemistry.chemical_classification, Behavior, Animal, General Neuroscience, digestive, oral, and skin physiology, Chromogranin A, Secretogranin II, MESH: Feeding Behavior, medicine.symptom, medicine.medical_specialty, endocrine system, MESH: Gene Expression, MESH: Rats, Hypothalamus, Neuropeptide, Biology, MESH: Food Deprivation, 03 medical and health sciences, Arcuate nucleus, Internal medicine, medicine, Animals, RNA, Messenger, MESH: Neuropeptide Y, Rats, Wistar, Gene, MESH: RNA, Messenger, MESH: Time Factors, RNA, Feeding Behavior, MESH: Rats, Wistar, MESH: Hypothalamus, Peptide Fragments, MESH: Male, Rats, 030104 developmental biology, Endocrinology, Mechanism of action, chemistry, biology.protein, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Secretogranin II, Food Deprivation, 030217 neurology & neurosurgery
Abstract

International audience; EM66 is a peptide derived from the chromogranin, secretogranin II (SG-II). Recent findings in mice indicate that EM66 is a novel anorexigenic neuropeptide that regulates hypothalamic feeding behavior, at least in part, by activating the POMC neurons of the arcuate nucleus. The present study aimed to investigate the mechanism of action of EM66 in the control of feeding behavior and, more specifically, its potential interactions with the NPY and POMC systems in rat. We analyzed by Q-PCR the gene expression of the EM66 precursor, SG-II, in hypothalamic extracts following 2, 3, or 4 days of food deprivation and compared it with the expression levels of the two major neuropeptidergic systems, that is, POMC and NPY, modulating feeding behavior. Our results show that fasting for 2 and 3 days has no effect on SG-II mRNA levels. However, 4 days of food deprivation induced a significant alteration in the expression levels of the three genes studied, with a significant increase in SG-II and NPY mRNAs, and conversely, a significant decrease in POMC mRNA. These data indicate that the EM66 gene expression is modulated by a negative energy status and suggest interactions between EM66 and NPY to regulate food intake through the POMC system.

Published
2017
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31. The octadecaneuropeptide ODN prevents 6-hydroxydopamine-induced apoptosis of cerebellar granule neurons through a PKC-MAPK-dependent pathway

Author

Laurence Desrues, Hubert Vaudry, Jérôme Leprince, Mohamed Amri, David Vaudry, Olfa Masmoudi-Kouki, Hadhemi Kaddour, Yosra Hamdi, Hélène Castel, Marie-Christine Tonon, M. Basille, Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Biological Sciences, Université de Tunis El Manar (UTM)-Laboratory of Functional Neurophysiology and Pathology, Research Unit UR/11ES09, Faculty of Science of Tunis-Faculty of Science of Tunis, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Télécom SudParis (TSP), and Université de Tunis El Manar (UTM)

Subjects
MAPK/ERK pathway, MESH: Cyclin D1, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Neurons, Apoptosis, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, medicine.disease_cause, Biochemistry, 0302 clinical medicine, Cerebellum, MESH: Caspase 3, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cyclin D1, MESH: Animals, Phosphorylation, MESH: Peptide Fragments, Protein Kinase C, Diazepam Binding Inhibitor, Neurons, MESH: Glutathione, 0303 health sciences, MESH: Oxidative Stress, Caspase 3, Chemistry, MESH: Reactive Oxygen Species, hemic and immune systems, MESH: Neuroprotective Agents, respiratory system, Glutathione, 3. Good health, Cell biology, Neuroprotective Agents, Programmed cell death, MESH: Rats, MAP Kinase Signaling System, Neuroprotection, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Animals, Rats, Wistar, Oxidopamine, Protein kinase C, 030304 developmental biology, Hydroxydopamine, MESH: Phosphorylation, MESH: MAP Kinase Signaling System, MESH: Apoptosis, Neuropeptides, MESH: Sympatholytics, MESH: Rats, Wistar, MESH: Protein Kinase C, Peptide Fragments, MESH: Cerebellum, Rats, MESH: Oxidopamine, Oxidative Stress, Metabotropic receptor, nervous system, Sympatholytics, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, Reactive Oxygen Species, 030217 neurology & neurosurgery, Oxidative stress
Abstract

International audience; Oxidative stress, induced by various neurodegenerative diseases, initiates a cascade of events leading to apoptosis, and thus plays a critical role in neuronal injury. In this study, we have investigated the potential neuroprotective effect of the octadecaneuropeptide (ODN) on 6-hydroxydopamine (6-OHDA)-induced oxidative stress and apoptosis in cerebellar granule neurons (CGN). ODN, which is produced by astrocytes, is an endogenous ligand for both central-type benzodiazepine receptors (CBR) and a metabotropic receptor. Incubation of neurons with subnanomolar concentrations of ODN (10⁻¹⁸ to 10⁻¹² M) inhibited 6-OHDA-evoked cell death in a concentration-dependent manner. The effect of ODN on neuronal survival was abrogated by the metabotropic receptor antagonist, cyclo₁₋₈ [DLeu⁵]OP, but not by a CBR antagonist. ODN stimulated polyphosphoinositide turnover and ERK phosphorylation in CGN. The protective effect of ODN against 6-OHDA toxicity involved the phospholipase C/ERK MAPK transduction cascade. 6-OHDA treatment induced an accumulation of reactive oxygen species, an increase of the expression of the pro-apoptotic gene Bax, a drop of the mitochondrial membrane potential and a stimulation of caspase-3 activity. Exposure of 6-OHDA-treated cells to ODN blocked all the deleterious effects of the toxin. Taken together, these data demonstrate for the first time that ODN is a neuroprotective agent that prevents 6-OHDA-induced oxidative stress and apoptotic cell death.

Published
2013
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32. Selenoprotein T Deficiency Leads to Neurodevelopmental Abnormalities and Hyperactive Behavior in Mice

Author

Gaëtan Prévost, Magalie Bénard, Matthieu T. Castex, Vadim Le Joncour, Arnaud Arabo, Anthony Falluel-Morel, Youssef Anouar, Jean-Jacques Bonnet, Vincent Roy, Institute for Research and Innovation in Biomedicine ( IRIB ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Psychologie et Neurosciences de la Cognition et de l'affectivité ( PSY-NCA ), Normandie Université ( NU ) -Normandie Université ( NU ), Différenciation et communication neuronale et neuroendocrine ( DC2N ), Neuroendocrinologie cellulaire et moléculaire, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Psychologie et Neurosciences de la Cognition et de l'affectivité (PSY-NCA), and Normandie Université (NU)-Normandie Université (NU)

Subjects
0301 basic medicine, medicine.medical_specialty, Cerebellum, Cell Survival, Neurogenesis, Neuroscience (miscellaneous), Hippocampus, Apoptosis, Biology, Hyperkinesis, Nervous System Malformations, Nervous System, Nestin, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, Conditional gene knockout, medicine, Animals, Homeostasis, Selenoproteins, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, Mice, Knockout, Neurons, Behavior, Animal, Integrases, [SCCO.NEUR]Cognitive science/Neuroscience, Brain, Selenoprotein T, Organ Size, Rats, Mice, Inbred C57BL, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Neurology, Animals, Newborn, Cerebral cortex, Astrocytes, Knockout mouse, [ SCCO.NEUR ] Cognitive science/Neuroscience, Neuron, Reactive Oxygen Species, Neuroscience, Oxidation-Reduction
Abstract

Selenoprotein T (SelT) is a newly discovered thioredoxin-like protein, which is abundantly but transiently expressed in the neural lineage during brain ontogenesis. Because its physiological function in the brain remains unknown, we developed a conditional knockout mouse line (Nes-Cre/SelTfl/fl) in which SelT gene is specifically disrupted in nerve cells. At postnatal day 7 (P7), these mice exhibited reduced volume of different brain structures, including hippocampus, cerebellum, and cerebral cortex. This phenotype, which is observed early during the first postnatal week, culminated at P7 and was associated with increased loss of immature neurons but not glial cells, through apoptotic cell death. This phenomenon was accompanied by elevated levels of intracellular reactive oxygen species, which may explain the increased neuron demise and reduced brain structure volumes. At the second postnatal week, an increase in neurogenesis was observed in the cerebellum of Nes-Cre/SelTfl/fl mice, suggesting the occurrence of developmental compensatory mechanisms in the brain. In fact, the brain volume alterations observed at P7 were attenuated in adult mice. Nevertheless, SelT mutant mice exhibited a hyperactive behavior, suggesting that despite an apparent morphological compensation, SelT deficiency leads to cerebral malfunction in adulthood. Altogether, these results demonstrate that SelT exerts a neuroprotective role which is essential during brain development, and that its loss impairs mice behavior.

Published
2016
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33. Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis

Author

Pierrick Gandolfo, Marie-Thérèse Schouft, Hélène Castel, Fabrice Morin, Céline Lecointre, Laurence Desrues, Nicolas Perzo, Pierre-Michaël Coly, Olivier Wurtz, Vadim Le Joncour, Marie-Christine Tonon, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Sherbrooke (UdeS), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Neuroendocrinologie cellulaire et moléculaire, and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Autophagosome, MESH: Chemotaxis, MESH: Calpain, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV]Life Sciences [q-bio], Autophagy-Related Proteins, MESH: Receptors, G-Protein-Coupled, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, Autophagy-Related Protein 5, Receptors, G-Protein-Coupled, MESH: Glioma, MESH: Autophagy-Related Proteins, Phosphatidylinositol 3-Kinases, Chemokine receptor, GPCR, Receptor, ComputingMilieux_MISCELLANEOUS, Brain Neoplasms, Calpain, chemotactic migration, Chemotaxis, TOR Serine-Threonine Kinases, Glioma, urotensin II, Endocytosis, Basic Research Paper, Cell biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MESH: HEK293 Cells, MESH: Brain Neoplasms, MESH: Endocytosis, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Receptors, CXCR4, MESH: Cell Line, Tumor, autophagosome biogenesis, MESH: Autophagosomes, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Receptors, CXCR4, MESH: Cell Adhesion, 03 medical and health sciences, Cell surface receptor, Cell Line, Tumor, Autophagy, Humans, MESH: Autophagy, Cell adhesion, Molecular Biology, MESH: TOR Serine-Threonine Kinases, G protein-coupled receptor, CXCR4, MESH: Humans, Autophagosomes, cell adhesion, Cell Biology, MESH: Autophagy-Related Protein 5, HEK293 Cells, 030104 developmental biology, MESH: Phosphatidylinositol 3-Kinases
Abstract

International audience; Chemotactic migration is a fundamental behavior of cells and its regulation is particularly relevant in physiological processes such as organogenesis and angiogenesis, as well as in pathological processes such as tumor metastasis. The majority of chemotactic stimuli activate cell surface receptors that belong to the G protein-coupled receptor (GPCR) superfamily. Although the autophagy machinery has been shown to play a role in cell migration, its mode of regulation by chemotactic GPCRs remains largely unexplored. We found that ligand-induced activation of 2 chemotactic GPCRs, the chemokine receptor CXCR4 and the urotensin 2 receptor UTS2R, triggers a marked reduction in the biogenesis of autophagosomes, in both HEK-293 and U87 glioblastoma cells. Chemotactic GPCRs exert their anti-autophagic effects through the activation of CAPNs, which prevent the formation of pre-autophagosomal vesicles from the plasma membrane. We further demonstrated that CXCR4- or UTS2R-induced inhibition of autophagy favors the formation of adhesion complexes to the extracellular matrix and is required for chemotactic migration. Altogether, our data reveal a new link between GPCR signaling and the autophagy machinery, and may help to envisage therapeutic strategies in pathological processes such as cancer cell invasion.

Published
2016
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34. Identification of three somatostatin genes in lampreys

Author

María Celina Rodicio, Boon-Hui Tay, Hervé Tostivint, Sylvie Mazan, Agnès Dettai, Natalia B. Kenigfest, Byrappa Venkatesh, Feng B. Quan, Vydianathan Ravi, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Systématique, adaptation, évolution (SAE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Evolution des régulations endocriniennes (ERE), Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS), Comparative Genomics Laboratory, Agency for Science, Technology and Research (A*STAR), International Institute of Molecular and Cell Biology, Mer et santé (MS), Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences [Moscow] (RAS), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)

Subjects
musculoskeletal diseases, 0301 basic medicine, DNA, Complementary, [SDV]Life Sciences [q-bio], Synteny, Evolution, Molecular, 03 medical and health sciences, Endocrinology, stomatognathic system, Phylogenetics, Animals, Amino Acid Sequence, skin and connective tissue diseases, Gene, Peptide sequence, Phylogeny, ComputingMilieux_MISCELLANEOUS, Sequence (medicine), Phylogenetic tree, biology, Base Sequence, Sequence Homology, Amino Acid, Lamprey, Lampreys, Actinistia, Anatomy, biology.organism_classification, eye diseases, stomatognathic diseases, 030104 developmental biology, Evolutionary biology, Animal Science and Zoology, Somatostatin
Abstract

Somatostatins (SSs) are a structurally diverse family of neuropeptides that play important roles in the regulation of growth, development and metabolism in vertebrates. It has been recently proposed that the common ancestor of gnathostomes possessed three SS genes, namely SS1, SS2 and SS5. SS1 and SS2 are still present in most extant gnathostome species investigated so far while SS5 primarily occurs in chondrichthyes, actinopterygians and actinistia but not in tetrapods. Very little is known about the repertoire of SSs in cyclostomes, which are extant jawless vertebrates. In the present study, we report the cloning of the cDNAs encoding three distinct lamprey SS variants that we call SSa, SSb and SSc. SSa and SSb correspond to the two SS variants previously characterized in lamprey, while SSc appears to be a totally novel one. SSa exhibits the same sequence as gnathostome SS1. SSb differs from SSa by only one substitution (Thr12 → Ser). SSc exhibits a totally unique structure (ANCRMFYWKTMAAC) that shares only 50% identity with SSa and SSb. SSa, SSb and SSc precursors do not exhibit any appreciable sequence similarity outside the C-terminal region containing the SS sequence. Phylogenetic analyses failed to clearly assign orthology relationships between lamprey and gnathostome SS genes. Synteny analysis suggests that the SSc gene arose before the split of the three gnathostome genes SS1, SS2 and SS5.

Published
2016
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35. PKA regulatory subunit 1A inactivating mutation induces serotonin signaling in primary pigmented nodular adrenal disease

Author

Bruno Ragazzon, Isabelle Boutelet, Julien Wils, Marthe Rizk-Rabin, Estelle Louiset, Zakariae Bram, Marie-Christine Vantyghem, Rossella Libé, Sylvie Renouf, Constantine A. Stratakis, Eva Szarek, Céline Duparc, Dennis A. Carson, Antoine Martinez, Jacques Young, Hervé Lefebvre, Jérôme Bertherat, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique, Reproduction et Développement - Clermont Auvergne (GReD), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), CHU Cochin [AP-HP], Récepteurs stéroïdiens : physiopathologie endocrinienne et métabolique, Université Paris-Sud - Paris 11 (UP11)-IFR93-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Endocrinologie et Métabolisme, Section on Endocrinology and Genetics, National Institutes of Health (NIH)-National Institute of Child Health and Human Development, Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR93-Université Paris-Sud - Paris 11 (UP11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (IC UM3 (UMR 8104 / U1016)), U693, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Sud (Paris 11), Recherche translationelle sur le diabète (EGID), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut Européen de Génomique du Diabète - EGID, Département d'Endocrinologie, Diabète et Maladies Métaboliques [CHU Rouen], Normandie Université (NU)-Normandie Université (NU), Recherche translationnelle sur le diabète - U 1190 (RTD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), ANR-06-MRAR-0002,Complexe de Carney,Physiopathologie et Génétique de la dysplasie micronodulaire pigmentée des surrénales (PPNAD) et du complexe de Carney (CNC).(2006), and ANR-08-GENO-0007,Complexe de Carney,Physiopathologie et génétique de la dysplasie micronodulaire pigmentée des surrénales (PPNAD) et du complexe de Carney (CNC)(2008)

Subjects
0301 basic medicine, Male, MESH: Signal Transduction, Receptor expression, [SDV]Life Sciences [q-bio], Tryptophan Hydroxylase, 0302 clinical medicine, MESH: Child, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Child, PRKAR1A, ComputingMilieux_MISCELLANEOUS, MESH: Middle Aged, TPH2, General Medicine, Middle Aged, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, MESH: Young Adult, Child, Preschool, Female, Signal transduction, Signal Transduction, Research Article, Adrenal Cortex Diseases, Adult, medicine.medical_specialty, Serotonin, MESH: Receptors, Serotonin, MESH: Mutation, Adolescent, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Serotonergic, Cell Line, 03 medical and health sciences, Young Adult, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, MESH: Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Protein kinase A, MESH: Adolescent, MESH: Humans, MESH: Adrenal Cortex Diseases, MESH: Child, Preschool, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Tryptophan hydroxylase, MESH: Male, MESH: Tryptophan Hydroxylase, MESH: Cell Line, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, 030104 developmental biology, Endocrinology, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, Receptors, Serotonin, Mutation, MESH: Serotonin, MESH: Female, Primary pigmented nodular adrenocortical disease
Abstract

International audience; Primary pigmented nodular adrenocortical disease (PPNAD) is a rare cause of ACTH-independent hypercortisolism. The disease is primarily caused by germline mutations of the protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene, which induces constitutive activation of PKA in adrenocortical cells. Hypercortisolism is thought to result from PKA hyperactivity, but PPNAD tissues exhibit features of neuroendocrine differentiation, which may lead to stimulation of steroidogenesis by abnormally expressed neurotransmitters. We hypothesized that serotonin (5-HT) may participate in the pathophysiology of PPNAD-associated hypercortisolism. We show that PPNAD tissues overexpress the 5-HT synthesizing enzyme tryptophan hydroxylase type 2 (Tph2) and the serotonin receptors types 4, 6, and 7, leading to formation of an illicit stimulatory serotonergic loop whose pharmacological inhibition in vitro decreases cortisol production. In the human PPNAD cell line CAR47, the PKA inhibitor H-89 decreases 5-HT4 and 5-HT7 receptor expression. Moreover, in the human adrenocortical cell line H295R, inhibition of PRKAR1A expression increases the expression of Tph2 and 5-HT4/6/7 receptors, an effect that is blocked by H-89. These findings show that the serotonergic process observed in PPNAD tissues results from PKA activation by PRKAR1A mutations. They also suggest that Tph inhibitors may represent efficient treatments of hypercortisolism in patients with PPNAD.

Published
2016
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36. CRISPR-Barcoding for Intratumor Genetic Heterogeneity Modeling and Functional Analysis of Oncogenic Driver Mutations

Author

Olivier Boyer, Hassan Ainani, Sathish Kumar Mungamuri, Anitha D. Jayaprakash, Sophie Coutant, Dorthe Cartier, Myriam Vezain, Françoise Charbonnier, David Alexandre, Ravi Sachidanandam, Stuart A. Aaronson, Shen Yao, Alexis Guernet, Isabelle Tournier, Guy Rohkin, Sahil Adriouch, Youssef Anouar, Luca Grumolato, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Oncological Sciences [New York, NY, USA], Icahn School of Medicine at Mount Sinai [New York] (MSSM), Neuroendocrinologie cellulaire et moléculaire, Cold Spring Harbor Laboratory, Physiopathologie et biothérapies des maladies inflammatoires et autoimmunes, Génétique du cancer et des maladies neuropsychiatriques (GMFC), Institute for Research and Innovation in Biomedicine (IRIB), Génomique et Médecine Personnalisée du Cancer et des Maladies Neuropsychiatriques (GPMCND), Laboratoire d'immunologie et biothérapies [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)

Subjects
0301 basic medicine, Male, Lung Neoplasms, Time Factors, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Mice, SCID, medicine.disease_cause, Genome editing, Carcinoma, Non-Small-Cell Lung, Antineoplastic Combined Chemotherapy Protocols, Tumor Microenvironment, CRISPR, Genetics, Gene Editing, Mutation, High-Throughput Nucleotide Sequencing, DNA, Neoplasm, ErbB Receptors, Phenotype, Editorial, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, MCF-7 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, [SDV.IB]Life Sciences [q-bio]/Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Biology, Article, 03 medical and health sciences, Genetic Heterogeneity, medicine, Biomarkers, Tumor, Animals, Humans, Point Mutation, Cell Lineage, Genetic Predisposition to Disease, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Protein Kinase Inhibitors, Dose-Response Relationship, Drug, Genetic heterogeneity, Cas9, Point mutation, Cancer, Cell Biology, Oncogenes, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, medicine.disease, HCT116 Cells, Xenograft Model Antitumor Assays, Clone Cells, 030104 developmental biology, HEK293 Cells, Drug Resistance, Neoplasm, CRISPR-Cas Systems, [SDV.IMM.VAC]Life Sciences [q-bio]/Immunology/Vaccinology, Multiplex Polymerase Chain Reaction
Abstract

International audience; Intratumor genetic heterogeneity underlies the abilityof tumors to evolve and adapt to different environ-mental conditions. Using CRISPR/Cas9 technologyand specific DNA barcodes, we devised a strategyto recapitulate and trace the emergence of subpopu-lations of cancer cells containing a mutation ofinterest. We used this approach to model differentmechanisms of lung cancer cell resistance to EGFRinhibitors and to assess effects of combined drugtherapies. By overcoming intrinsic limitations of cur-rent approaches, CRISPR-barcoding also enablesinvestigation of most types of genetic modifications,including repair of oncogenic driver mutations.Finally, we used highly complex barcodes insertedat a specific genome location as a means of simulta-neously tracing the fates of many thousands ofgenetically labeled cancer cells. CRISPR-barcodingis a straightforward and highly flexible method thatshould greatly facilitate the functional investigation ofspecific mutations, in a context that closely mimicsthe complexity of cancer

Published
2016
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37. Delayed PACAP delivery after brain stroke improves functional recovery by inducing M2 microglia/macrophage polarization

Author

Brifault, Coralie, Gras, Marjorie, Liot, Donovan, May, Victor, Vaudry, David, Wurtz, Olivier, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Vermont College of Medicine, Différenciation et communication neuronale et neuroendocrine (DC2N), University of Vermont [Burlington], and Wurtz, Olivier

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2016

38. The Spinal Cord Has an Intrinsic System for the Control of pH

Author

Sten Grillner, Brita Robertson, Peter Wallén, Elham Jalalvand, Hervé Tostivint, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Male, Physiology, Receptors, Cell Surface, Biology, General Biochemistry, Genetics and Molecular Biology, Membrane Potentials, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, CSF-c neuron, Receptor, alpha-stat, ComputingMilieux_MISCELLANEOUS, Membrane potential, Voltage-dependent calcium channel, General Commentary, pH, Antagonist, Lampreys, spinal cord, temperature, Anatomy, Sequence Analysis, DNA, Hydrogen-Ion Concentration, Spinal cord, 030104 developmental biology, Somatostatin, medicine.anatomical_structure, Biophysics, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neuron, Calcium Channels, General Agricultural and Biological Sciences, 030217 neurology & neurosurgery, Homeostasis, Locomotion
Abstract

For survival of the organism, acid-base homeostasis is vital [1, 2]. The respiratory and renal systems are central to this control. Here we describe a novel mechanism, intrinsic to the spinal cord, with sensors that detect pH changes and act to restore pH to physiological levels by reducing motor activity. This pH sensor consists of somatostatin-expressing cerebrospinal fluid-contacting (CSF-c) neurons, which target the locomotor network. They have a low level of activity at pH 7.4. However, at both alkaline and acidic pH, the activity of the individual CSF-c neuron is markedly enhanced through the action of two separate channel subtypes. The alkaline response depends on PKD2L1 channels that have a large conductance and an equilibrium potential around 0 mV, both characteristics of mouse PKD2L1 channels [3-5]. The acidic response is due to an activation of ASIC3 [6]. The discharge pattern of the CSF-c neurons is U-shaped with a minimum frequency around pH 7.4 and a marked increase already at slightly lower and higher pH. During ongoing locomotor activity in the isolated spinal cord, both an increase and as a decrease of pH will reduce the locomotor burst rate. A somatostatin antagonist blocks these effects, suggesting that CSF-c neurons are responsible for the suppression of locomotor activity. CSF-c neurons thus represent a novel innate homeostatic mechanism, designed to sense any deviation from physiological pH and to respond by causing a depression of the motor activity. Because CSF-c neurons are found in all vertebrates, their pH-sensing function is most likely conserved.

Published
2016
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39. Differences in parvalbumin and calbindin chemospecificity in the centers of the turtle ascending auditory pathway revealed by double immunofluorescence labeling

Author

Hervé Tostivint, Natalia B. Kenigfest, M. G. Belekhova, Roger Ward, T. V. Chudinova, Jean-Paul Rio, Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences [Moscow] (RAS), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de psychologie [Trois-Rivières], Université du Québec à Trois-Rivières (UQTR), Developpement Normal et Pathologique du Cerveau, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Calbindins, Auditory Pathways, Fluorescent Antibody Technique, Calbindin, Cochlear nucleus, 03 medical and health sciences, S100 Calcium Binding Protein G, 0302 clinical medicine, mental disorders, medicine, Animals, Molecular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Brain Chemistry, Neurons, 0303 health sciences, biology, musculoskeletal, neural, and ocular physiology, General Neuroscience, digestive, oral, and skin physiology, Brain, Turtles, Cell biology, Parvalbumins, medicine.anatomical_structure, nervous system, Superior olivary complex, Forebrain, biology.protein, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Nucleus reuniens, Neurology (clinical), Brainstem, Neuroscience, Nucleus, 030217 neurology & neurosurgery, Parvalbumin, Developmental Biology
Abstract

Using double immunofluorescence labeling, quantitative ratio between parvalbumin- and calbindin-containing neurons, neurons that co-localize both peptides, as well as the intensity of their immunoreactivities were studied in the brainstem, midbrain and forebrain auditory centers of two chelonian species, Testudo horsfieldi and Emys orbicularis. In the spiral ganglion and first-order cochlear nuclei, highly immunoreactive parvalbumin-containing neurons predominated, and almost all neurons in these nuclei also exhibited weak immunoreactivity to calbindin. The number of strongly calbindin-immunoreactive (-ir) cells increased in the second-order brainstem auditory centers (the laminar cochlear nucleus, superior olivary complex, lateral lemniscal nucleus), and co-localization with parvalbumin in some of them was observed. In the midbrain, a complementary distribution of parvalbumin and calbindin immunoreactivity was found: the central (core) region of the torus semicircularis showed strong parvalbumin immunoreactivity, while the laminar (belt) nucleus was strongly calbindin-ir. In the thalamic nucleus reuniens, almost complete topographic overlapping of the parvalbumin-ir and calbindin-ir neurons was shown in its dorsomedial region (core), with the intensity of immunoreactivity to calbindin being much higher than that to parvalbumin. The predominance of calbindin immunoreactivity in neurons of the dorsomedial region of the nucleus reuniens is correlated with the existence of the dense calbindin-ir terminal field in its projection area in the telencephalon. We conclude that the turtle auditory pathway is chemically heterogeneous with respect to calcium-binding proteins, the predominance of parvalbumin in the brainstem and midbrain centers giving way to that of calbindin in the forebrain centers; the portion of neurons co-localizing both peptides nonlinearly decreases from lower to higher order centers.

Published
2012
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40. Pituitary adenylate cyclase-activating polypeptide and vasoactive intestinal polypeptide promote the genesis of calcium currents in differentiating mouse embryonic stem cells

Author

Pierre Gressens, M. Chafai, William Rostène, Hubert Vaudry, M. Basille, Bruno J. Gonzalez, Estelle Louiset, Ludovic Galas, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagerie cellulaire des neurorécepteurs et physiopathologie neuroendocrinienne, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Normandie Université (NU), and Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
MESH: Cell Differentiation, MESH: Neural Stem Cells, Neurogenesis, Cellular differentiation, Vasoactive intestinal peptide, Biology, Real-Time Polymerase Chain Reaction, Mice, MESH: Gene Expression Profiling, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, MESH: Reverse Transcriptase Polymerase Chain Reaction, MESH: Gene Expression Regulation, Developmental, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, MESH: Animals, L-type calcium channel, MESH: Embryonic Stem Cells, MESH: Mice, Embryonic Stem Cells, 030304 developmental biology, 0303 health sciences, Voltage-dependent calcium channel, Reverse Transcriptase Polymerase Chain Reaction, MESH: Real-Time Polymerase Chain Reaction, Gene Expression Profiling, General Neuroscience, Calcium channel, MESH: Pituitary Adenylate Cyclase-Activating Polypeptide, MESH: Vasoactive Intestinal Peptide, T-type calcium channel, Gene Expression Regulation, Developmental, Cell Differentiation, MESH: Immunohistochemistry, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Immunohistochemistry, Embryonic stem cell, Molecular biology, Neural stem cell, MESH: Neurogenesis, 3. Good health, MESH: Calcium Channels, Pituitary Adenylate Cyclase-Activating Polypeptide, Calcium Channels, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery, Vasoactive Intestinal Peptide
Abstract

International audience; Identification of novel molecules that can induce neuronal differentiation of embryonic stem (ES) cells is essential for deciphering the molecular mechanisms of early development and for exploring cell therapy approaches. Pituitary adenylate cyclase-activating polypeptide (PACAP) and vasoactive intestinal polypeptide (VIP) are known to be implicated early during ontogenesis in cell proliferation and neuronal differentiation. The aim of the present study was to determine the effects of VIP and PACAP on functional differentiation of ES cells. Quantitative-reverse transcription-polymerase chain reaction analysis showed an inversion of the expression pattern of PAC1 and VPAC1 receptors with time. ES cells expressed genes encoding extracellular signal-regulated kinase 1 and 2 and c-jun amino terminal kinase1. ES cells also expressed T-type α1I and α1G, L-type α1C and α1D, and N-type α1B calcium channel subunit mRNAs. Both peptides modified the shape of undifferentiated ES cells into bipolar cells expressing the neuronal marker neuron-specific enolase (NSE). Immunostaining indicated that PACAP intensified T-type α1I subunit immunoreactivity, whereas VIP increased L-types α1C and α1D, as well as N-type α1B subunit. Electrophysiological recording showed that VIP and PACAP enhanced transient calcium current. Moreover, VIP generated sustained calcium current. These findings demonstrate that PACAP and VIP induce morphological and functional differentiation of ES cells into a neuronal phenotype. Both peptides promote functional maturation of calcium channel subunits, suggesting that they can facilitate the genesis of cellular excitability.

Published
2011
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41. Structure–Activity Relationships of a Series of Analogues of the RFamide-Related Peptide 26RFa

Author

Le Marec, Olivier, Neveu, Cindy, Lefranc, Benjamin, Dubessy, Christophe, Boutin, Jean, Do-Régo, Jean, Costentin, Jean, Tonon, Marie-Christine, Tena-Sempere, Manuel, Vaudry, Hubert, Do-Régo, Jean, Leprince, Jérôme, EPSM-Morbihan, Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherches Servier, Centre de Recherches de Croissy, Neuropsycho-pharmacologie expérimentale, Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Department of Cell Biology, and Neuroendocrinologie cellulaire et moléculaire

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Cricetinae, Peptide, MESH: Amino Acid Sequence, MESH: Receptors, G-Protein-Coupled, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Ligands, MESH: Neuropeptides, Receptors, G-Protein-Coupled, MESH: GTP-Binding Protein beta Subunits, chemistry.chemical_compound, MESH: Structure-Activity Relationship, 0302 clinical medicine, MESH: Cricetulus, Cricetinae, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Drug Discovery, MESH: Ligands, MESH: Animals, Peptide sequence, Alanine, chemistry.chemical_classification, 0303 health sciences, GTP-Binding Protein beta Subunits, Stereoisomerism, Gonadotropin secretion, Biochemistry, MESH: Calcium, Molecular Medicine, Stereochemistry, CHO Cells, Transfection, Structure-Activity Relationship, 03 medical and health sciences, Cricetulus, MESH: CHO Cells, Animals, Structure–activity relationship, Amino Acid Sequence, 030304 developmental biology, G protein-coupled receptor, MESH: Transfection, Neuropeptides, Rational design, MESH: Stereoisomerism, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Calcium, Norvaline, 030217 neurology & neurosurgery
Abstract

International audience; 26RFa is a new member of the RFamide peptide family that has been identified as the endogenous ligand of the orphan GPCR GPR103. As the C-terminal heptapeptide (26RFa((20-26))) mimics the action of the native peptide on food intake and gonadotropin secretion in rodents, we have synthesized a series of analogues of 26RFa((20-26)) and measured their potency to induce [Ca(2+)](i) mobilization in Gα(16)-hGPR103-transfected CHO cells. Systematic replacement of each residue by an alanine (Ala scan) and its D-enantiomer (D scan) showed that the last three C-terminal residues were very sensitive to the substitutions while position 23 tolerated rather well both modifications. Most importantly, replacement of Ser(23) by a norvaline led to an analogue, [Nva(23)]26RFa((20-26)), that was 3-fold more potent than the native heptapeptide. These new pharmacological data, by providing the first information regarding the structure-activity relationships of 26RFa analogues, should prove useful for the rational design of potent GPR103 receptor ligands with potential therapeutic application.

Published
2011
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42. Purification and properties of antimicrobial peptides from skin secretions of the Eritrea clawed frog Xenopus clivii (Pipidae)

Author

Conlon, J Michael, Mechkarska, Milena, Ahmed, Eman, Leprince, Jérôme, Vaudry, Hubert, King, Jay, Takada, Koji, Conlon, J. Michael, Faculty of Medicine and Health Science, UAE University, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Différenciation et communication neuronale et neuroendocrine (DC2N)

Subjects
Male, Physiology, Xenopus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Health, Toxicology and Mutagenesis, Pipidae, Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Xenopus Proteins, Toxicology, Biochemistry, chemistry.chemical_compound, Anti-Infective Agents, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Staphylococcus aureus, MESH: Animals, MESH: Xenopus, Xenopus clivii, MESH: Xenopus Proteins, Skin, chemistry.chemical_classification, MESH: Microbial Sensitivity Tests, 0303 health sciences, biology, MESH: Escherichia coli, 030302 biochemistry & molecular biology, MESH: Antimicrobial Cationic Peptides, General Medicine, Antimicrobial, Female, Staphylococcus aureus, MESH: Anti-Infective Agents, Antimicrobial peptides, Microbial Sensitivity Tests, Microbiology, 03 medical and health sciences, MESH: Skin, Drug Resistance, Bacterial, MESH: Drug Resistance, Bacterial, Escherichia coli, Animals, 030304 developmental biology, Magainin, Cell Biology, biology.organism_classification, MESH: Male, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Female, Frog Skin, Antimicrobial Cationic Peptides
Abstract

International audience; Five peptides with antimicrobial activity were isolated from norepinephrine-stimulated skin secretions of the tetraploid frog Xenopus clivii Peracca, 1898 (Pipidae). Characterization of the peptides demonstrated that they are structurally similar to magainins (2 peptides), caerulein-precursor fragments, CPF (2 peptides), and xenopsin-precursor fragments, XPF (1 peptide) that have been previously isolated from other species of the genus Xenopus. The magainins and the XPF peptide were active only against the Gram-negative microorganism Escherichia coli whereas the CPF peptides were also active against the Gram-positive Staphylococcus aureus. The most abundant antimicrobial peptide in the secretions, CPF-C1 (GFGSLLGKALRLG ANVL.NH(2)) inhibited the growth of the Gram-negative bacteria Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa (MIC≤25μM) suggesting potential for development into an anti-infective agent for use against these emerging antibiotic-resistant pathogens.

Published
2011
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43. Characterization of antimicrobial peptides in skin secretions from discrete populations of Lithobates chiricahuensis (Ranidae) from central and southern Arizona

Author

Conlon, J Michael, Mechkarska, Milena, Coquet, Laurent, Jouenne, Thierry, Leprince, Jérôme, Vaudry, Hubert, Kolodziejek, Jolanta, Nowotny, Norbert, King, Jay, Conlon, J. Michael, Faculty of Medicine and Health Science, UAE University, Polymères, biopolymères, membranes (PBM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), and Zoonoses and Emerging Infections Group

Subjects
Erythrocytes, Ranidae, MESH: Sequence Homology, Amino Acid, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Amino Acid Sequence, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Biochemistry, 0302 clinical medicine, Endocrinology, Anti-Infective Agents, Salientia, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Skin, Antibacterial agent, MESH: Microbial Sensitivity Tests, 0303 health sciences, MESH: Ranidae, biology, MESH: Peptides, Ecology, MESH: Erythrocytes, Arizona, MESH: Hemolysis, Taxonomy (biology), Mitochondrial DNA, Molecular Sequence Data, MESH: Anti-Infective Agents, Antimicrobial peptides, Zoology, Microbial Sensitivity Tests, Hemolysis, Lithobates chiricahuensis, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Skin, Animals, Humans, Amino Acid Sequence, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, Sequence Homology, Amino Acid, Leopard frog, biology.organism_classification, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Peptides, Frog Skin, 030217 neurology & neurosurgery, MESH: Arizona
Abstract

International audience; Populations of the Chiricahua leopard frog Lithobates chiricahuensis (Ranidae) occupying regions in southern Arizona (southern range) are morphologically distinct from those from the Mogollon Rim of central Arizona (northern range) and a comparison of DNA sequences of mitochondrial genes has suggested that they may represent separate species. Peptidomic analysis of norepinephrine-stimulated skin secretions has led to the identification of six peptides with antimicrobial activity in samples from specimens from both groups. The primary structure of the peptides (esculentin-2 CHa, ranatuerin-2 CHa, -CHb, and -CHc, and brevinin-1 CHa and -CHb) isolated from both southern and northern range frogs are identical consistent with the proposal that the two populations are conspecific. However, palustrin-2CHa and the atypical brevinin-1 CHc (FFPTIAG*****LTKLFCA ITKKC), containing a five amino acid residue deletion, were identified only in secretions from southern range specimens. Consequently, there is some support for the proposal that the two populations are closely related but separate species but this support is relatively weak. Esculentin-2 CHa (GFSSIFRGVAKFASKGLG KDLAKLGVDLVACKISKQC) displayed the highest antimicrobial potency (MIC ≤ 10μM) against a variety of microorganisms and was only moderately hemolytic (LC(50) = 150 μM). Cladistic analysis based upon the primary structures of brevinin-1 peptides indicates a close phylogenetic relationship between L. chiricahuensis, L. onca, and L. yavapaiensis.

Published
2011
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44. Temperature-Responsive Polymer Brushes Switching from Bactericidal to Cell-Repellent

Author

Emilie Fautré, Xavier Laloyaux, Jérôme Leprince, Alain M. Jonas, Karine Glinel, Viswas Purohit, Thomas Blin, Thierry Jouenne, Institut des Sciences Chimiques de Rennes (ISCR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut Ecologie et Environnement (INEE), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Polymères, biopolymères, membranes (PBM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Université Catholique de Louvain = Catholic University of Louvain (UCL), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Materials science, Surface Properties, Xenopus, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Nanotechnology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, Xenopus Proteins, MESH: Ethylene Glycols, 010402 general chemistry, 01 natural sciences, MESH: Transition Temperature, Coated Materials, Biocompatible, MESH: Coated Materials, Biocompatible, MESH: Anti-Bacterial Agents, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Animals, Transition Temperature, MESH: Animals, MESH: Xenopus, General Materials Science, Thin film, MESH: Xenopus Proteins, ComputingMilieux_MISCELLANEOUS, MESH: Surface Properties, Bacteria, Mechanical Engineering, Transition temperature, Temperature, MESH: Antimicrobial Cationic Peptides, 021001 nanoscience & nanotechnology, MESH: Methacrylates, MESH: Temperature, Anti-Bacterial Agents, 0104 chemical sciences, MESH: Bacteria, Mechanics of Materials, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Methacrylates, Surface modification, Ethylene Glycols, 0210 nano-technology, Antimicrobial Cationic Peptides, Temperature-responsive polymer
Abstract

International audience

Published
2010
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45. Characterization of a novel LFRFamide neuropeptide in the cephalopod Sepia officinalis

Author

Jérôme Leprince, Hubert Vaudry, Céline Zatylny-Gaudin, Joël Henry, Benoit Bernay, Bruno Zanuttini, Biologie des Organismes et Ecosystèmes Aquatiques (BOREA), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Muséum national d'Histoire naturelle (MNHN)-Institut de Recherche pour le Développement (IRD)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Laboratoire de Physiogénomique / NeuroTranscriptomes et Paléogénétique (LPG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Equipe MAD - Laboratoire GREYC - UMR6072, Groupe de Recherche en Informatique, Image et Instrumentation de Caen (GREYC), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Centre de recherche en gestion (CRG), Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X), Normandie Université (NU)-Normandie Université (NU)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), and École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Central Nervous System, Male, Cuttlefish, Sepia, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Amino Acid Sequence, MESH: Muscle, Smooth, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Oviducts, MESH: Neuropeptides, Biochemistry, 0302 clinical medicine, Endocrinology, MESH: Rectum, MESH: FMRFamide, Tandem Mass Spectrometry, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Hemolymph, MESH: Animals, Peptide sequence, Nerve Endings, 0303 health sciences, MESH: Sepia, MESH: Nerve Endings, Muscle Tonus, MESH: Oligopeptides, Officinalis, Female, MESH: Animal Structures, Oligopeptides, Spectrometry, Mass, Electrospray Ionization, medicine.medical_specialty, Neuropeptide, Biology, MESH: Spectrometry, Mass, Electrospray Ionization, 03 medical and health sciences, Cellular and Molecular Neuroscience, Internal medicine, medicine, MESH: Central Nervous System, Animals, Amino Acid Sequence, FMRFamide, 030304 developmental biology, Neuropeptides, Rectum, MESH: Tandem Mass Spectrometry, Animal Structures, Muscle, Smooth, MESH: Muscle Tonus, biology.organism_classification, MESH: Male, Cephalopod, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Female, MESH: Oviducts, 030217 neurology & neurosurgery
Abstract

International audience; From a single LC-MS/MS analysis, a new C-terminally extended RFamide neuropeptide was characterized in Sepia officinalis. The experimental strategy was based on the specific neutral loss associated with RFamide breakdown. Mass losses of 17 Da (C-terminally amide) and 320 Da (RFamide) have been observed for three known peaks of m/z 581.7 (FLRFamide), 599.8 (FMRFamide), 1096.3 (ALSGDAFLRFamide) and one unknown of m/z 752.8. The primary sequence of the peptide of m/z 752.8 was GNLFRFamide. MS/MS analyses revealed that this novel neuropeptide, called sepFRF1, is largely distributed in the central nervous system of cuttlefish of both sexes. Probably transported in the visceral nerve from the subesophageal mass (the peptide was not detected in the hemolymph), this neuropeptide targeted the rectum in agreement with its peripheral distribution. From concentrations as low as 10(-9)M, sepFRF1 increased the frequency, tonus and amplitude of rectal contractions. SepFRF1 is the first RFamide peptide identified in Sepia officinalis that is not derived from the FaRPs precursor. SepFRF1 could belong to a RFamide subfamily identified in gastropods and may be involved in feeding behavior.

Published
2010
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46. Beta-amyloid peptide stimulates endozepine release in cultured rat astrocytes through activation ofN-formyl peptide receptors

Author

Hélène Castel, Tursonjan Tokay, Mohamed Amri, Pierrick Gandolfo, Marie Christine Tonon, Hubert Vaudry, Olfa Masmoudi-Kouki, Raya Hachem, Jérôme Leprince, Mickaël Diallo, Laurence Desrues, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Faculté des Sciences Mathématiques, Physiques et Naturelles de Tunis (FST), and Université de Tunis El Manar (UTM)

Subjects
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Receptors, Formyl Peptide, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, MESH: Neuropeptides, Adenylyl cyclase, chemistry.chemical_compound, 0302 clinical medicine, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, MESH: Peptide Fragments, Receptor, Cells, Cultured, Protein Kinase C, Diazepam Binding Inhibitor, 0303 health sciences, MESH: Amyloid beta-Peptides, Cell biology, Neurology, medicine.symptom, MESH: Cells, Cultured, Endozepine, MESH: Rats, MESH: Receptor Cross-Talk, MESH: Cyclic AMP-Dependent Protein Kinases, Biology, 03 medical and health sciences, Cellular and Molecular Neuroscience, mental disorders, medicine, Animals, Rats, Wistar, Protein kinase A, Protein kinase C, 030304 developmental biology, Amyloid beta-Peptides, Phospholipase C, Neuropeptides, MESH: Rats, Wistar, Receptor Cross-Talk, MESH: Protein Kinase C, Cyclic AMP-Dependent Protein Kinases, Receptors, Formyl Peptide, Molecular biology, Peptide Fragments, Rats, MESH: Astrocytes, Chelerythrine, Mechanism of action, chemistry, Astrocytes, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Diazepam Binding Inhibitor, 030217 neurology & neurosurgery
Abstract

International audience; Astroglial cells synthesize and release endozepines, a family of neuropeptides derived from diazepam-binding inhibitor (DBI). The authors have recently shown that beta-amyloid peptide (Abeta) stimulates DBI gene expression and endozepine release. The purpose of this study was to determine the mechanism of action of Abeta in cultured rat astrocytes. Abeta(25-35) and the N-formyl peptide receptor (FPR) agonist N-formyl-Met-Leu-Phe (fMLF) increased the secretion of endozepines in a dose-dependent manner with EC(50) value of approximately 2 microM. The stimulatory effects of Abeta(25-35) and the FPR agonists fMLF and N-formyl-Met-Met-Met (fMMM) on endozepine release were abrogated by the FPR antagonist N-t-Boc-Phe-Leu-Phe-Leu-Phe. In contrast, Abeta(25-35) increased DBI mRNA expression through a FPR-independent mechanism. Abeta(25-35) induced a transient stimulation of cAMP formation and a sustained activation of polyphosphoinositide turnover. The stimulatory effect of Abeta(25-35) on endozepine release was blocked by the adenylyl cyclase inhibitor somatostatin, the protein kinase A (PKA) inhibitor H89, the phospholipase C inhibitor U73122, the protein kinase C (PKC) inhibitor chelerythrine and the ATP binding cassette transporter blocker glyburide. Taken together, these data demonstrate for the first time that Abeta(25-35) stimulates endozepine release from rat astrocytes through a FPR receptor positively coupled to PKA and PKC.

Published
2008
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47. Peroxiredoxin 2 is Involved in the Neuroprotective Effects of PACAP in Cultured Cerebellar Granule Neurons

Author

Alain Fournier, Pascal Cosette, David Vaudry, Magalie Bénard, Béatrice Botia, Aurélia Ravni, Bruno J. Gonzalez, Anthony Falluel-Morel, Damien Seyer, Hubert Vaudry, Thierry Jouenne, Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), International Associated laboratory Samuel de Champlain, Institut National de la Recherche Scientifique [Québec] (INRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), and This work was supported by INSERM (U413), the European Institute for Peptide Research (IFRMP23), the Institut de Recherches Scientifiques sur les Boissons (IREB), an Interreg 3A FEDER project, the ANR (06-JCJC-0071), and the Conseil Régional de Haute-Normandie. The work was conducted with the technical support of the proteomic facility of the IFRMP23 and the Platform for Cell Imaging of Haute-Normandie. BB was a recipient of a doctoral fellowship from the Société Française d’Alcoologie and a fellowship from the Fondation pour la Recherche Médicale. We thank Dr Mickaël Naassila for the quantification of ethanol level in blood samples.

Subjects
Small interfering RNA, [SDV]Life Sciences [q-bio], MESH: RNA, Small Interfering/genetics, MESH: Cerebellum/cytology, MESH: Amino Acid Sequence, 0302 clinical medicine, Cerebellum, MESH: Animals, RNA, Small Interfering, Cells, Cultured, MESH: Neurons/cytology, Neurons, 0303 health sciences, biology, medicine.diagnostic_test, Caspase 3, MESH: Pituitary Adenylate Cyclase-Activating Polypeptide/metabolism, General Medicine, respiratory system, 3. Good health, Neuroprotective Agents, MESH: Colforsin/metabolism, Pituitary Adenylate Cyclase-Activating Polypeptide, Tetradecanoylphorbol Acetate, hormones, hormone substitutes, and hormone antagonists, MESH: Cells, Cultured, Neurotrophin, endocrine system, MESH: Rats, Molecular Sequence Data, MESH: Neuroprotective Agents/metabolism, Adenylate kinase, Peroxiredoxin 2, Neuroprotection, MESH: Peroxiredoxins/metabolism, MESH: Ethanol/metabolism, 03 medical and health sciences, Cellular and Molecular Neuroscience, Western blot, MESH: Peroxiredoxins/genetics, medicine, Animals, Amino Acid Sequence, Rats, Wistar, Protein kinase C, 030304 developmental biology, MESH: Molecular Sequence Data, Ethanol, Colforsin, MESH: Neurons/metabolism, Peroxiredoxins, MESH: Rats, Wistar, Molecular biology, Rats, MESH: Tetradecanoylphorbol Acetate/metabolism, MESH: RNA, Small Interfering/metabolism, biology.protein, MESH: Pituitary Adenylate Cyclase-Activating Polypeptide/genetics, MESH: Caspase 3/metabolism, 030217 neurology & neurosurgery
Abstract

International audience; The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) is known to counteract in vitro the deleterious effects of toxic agents on cerebellar granule cell survival and differentiation. The potent antiapoptotic action of PACAP is mediated through inhibition of caspase-3 activity; however, additional proteins are likely involved and remain to be identified. Two-dimensional gel electrophoresis analysis coupled with mass spectrometry characterization led to the identification of a protein, peroxiredoxin 2, which was induced after a 6-h treatment with PACAP. Western blot analysis confirmed the regulation of peroxiredoxin 2 by PACAP and revealed that this protein is induced by both cyclic AMP and protein kinase C stimulators. Inhibition of peroxiredoxin 2 expression, using two distinct small-interfering RNAs (siRNAs), reduced the effect of PACAP on caspase-3 activity and cerebellar granule cell survival. Peroxiredoxin 2 expression was also induced in vivo and in vitro by ethanol. Although ethanol and PACAP exert opposite effects on caspase-3 activity, inhibition of peroxiredoxin 2 expression, using siRNAs, only reduced the ability of PACAP to prevent ethanol-induced caspase-3 activity. Taken together, these data indicate that peroxiredoxin 2 is probably involved in the neurotrophic effect of PACAP and suggest that this protein may have a therapeutic potential for the treatment of some neurodegenerative diseases

Published
2008
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48. Comparative distribution of the mRNAs encoding urotensin I and urotensin II in zebrafish

Author

Hélène Hardin-Pouzet, Emilie Hameury, André Calas, Hubert Vaudry, Jacques Taxi, Caroline Parmentier, Isabelle Lihrmann, Hervé Tostivint, Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Différenciation et communication neuronale et neuroendocrine (DC2N), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroplasticité des comportements de reproduction = Neuroplasticity of Reproductive Behaviors (NPS-11), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Neuroendocrinologie cellulaire et moléculaire, UA 339 Laboratoire de Physiologie des Interactions Cellulaires, Centre National de la Recherche Scientifique (CNRS), Neurobiologie des signaux intercellulaires (NSI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Recherches Multidisciplinaires sur les Peptides (IFRMP 23), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université Le Havre Normandie (ULH), Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), CHU Rouen, Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), and Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre de Lutte Contre le Cancer Henri Becquerel Normandie Rouen (CLCC Henri Becquerel)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Physiology, Urotensins, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Neuropeptide, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], In situ hybridization, Biology, Biochemistry, 03 medical and health sciences, Cellular and Molecular Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, medicine, Animals, Humans, Protein Isoforms, Tissue Distribution, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, RNA, Messenger, Gene, Zebrafish, ComputingMilieux_MISCELLANEOUS, Cellular localization, 030304 developmental biology, 0303 health sciences, Caudal neurosecretory system, Spinal cord, biology.organism_classification, Molecular biology, medicine.anatomical_structure, Spinal Cord, chemistry, Female, Urotensin-II, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

The neural neurosecretory system of fishes produces two biologically active neuropeptides, i.e. the corticotropin-releasing hormone paralog urotensin I (UI) and the somatostatin-related peptide urotensin II (UII). In zebrafish, we have recently characterized two UII variants termed UIIalpha and UIIbeta. In the present study, we have investigated the distribution of UI, UIIalpha and UIIbeta mRNAs in different organs by quantitative RT-PCR analysis and the cellular localization of the three mRNAs in the spinal cord by in situ hybridization (ISH) histochemistry. The data show that the UI gene is mainly expressed in the caudal portion of the spinal cord and, to a lesser extent, in the brain, while the UIIalpha and the UIIbeta genes are exclusively expressed throughout the spinal cord. Single-ISH labeling revealed that UI, UIIalpha and UIIbeta mRNAs occur in large cells, called Dahlgren cells, located in the ventral part of the caudal spinal cord. Double-ISH staining showed that UI, UIIalpha and UIIbeta mRNAs occur mainly in distinct cells, even though a few cells were found to co-express the UI and UII genes. The differential expression of UI, UIIalpha and UIIbeta genes may contribute to the adaptation of Dahlgren cell activity during development and/or in various physiological conditions.

Published
2008
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49. Structure–activity relationships of urotensin II and URP

Author

Hubert Vaudry, David Chatenet, Daniel Davoust, Pierre Pacaud, Christophe Dubessy, Laure Guilhaudis, Alain Fournier, Bruno Pfeiffer, Hassan Oulyadi, Marie-Christine Tonon, Jérôme Leprince, Pierre Renard, Elizabeth Scalbert, Isabelle Ségalas-Milazzo, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Montreal Heart Institute (MONTREAL HEART INSTITUTE), Les Laboratoires SERVIER, Institut de Recherche Servier, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Equipe de Chimie Organique et Biologie Structurale (ECOBS), Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)

Subjects
Protein Conformation, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Peptide Hormones, Peptide, Endogeny, MESH: Amino Acid Sequence, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Biochemistry, MESH: Tyrosine, chemistry.chemical_compound, MESH: Protein Conformation, MESH: Structure-Activity Relationship, 0302 clinical medicine, Endocrinology, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], MESH: Animals, Disulfides, MESH: Peptide Fragments, Receptor, chemistry.chemical_classification, 0303 health sciences, Alanine, Molecular Structure, Biological activity, 3. Good health, Amino acid, MESH: Alanine, Urotensins, MESH: Molecular Structure, Molecular Sequence Data, MESH: Sequence Alignment, Structure-Activity Relationship, 03 medical and health sciences, Cellular and Molecular Neuroscience, Animals, Humans, Structure–activity relationship, MESH: Disulfides, Amino Acid Sequence, Cysteine, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, MESH: Urotensins, Rational design, MESH: Cysteine, Peptide Fragments, chemistry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Peptide Hormones, Tyrosine, Urotensin-II, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

International audience; Urotensin II (U-II) and urotensin II-related peptide (URP) are the endogenous ligands for the orphan G-protein-coupled receptor GPR14 now renamed UT. At the periphery, U-II and/or URP exert a wide range of biological effects on cardiovascular tissues, airway smooth muscles, kidney and endocrine glands, while central administration of U-II elicits various behavioral and cardiovascular responses. There is also evidence that U-II and/or URP may be involved in a number of pathological conditions including heart failure, atherosclerosis, renal dysfunction and diabetes. Because of the potential involvement of the urotensinergic system in various physiopathological processes, there is need for the rational design of potent and selective ligands for the UT receptor. Structure-activity relationship studies have shown that the minimal sequence required to retain full biological activity is the conserved U-II(4-11) domain, in particular the Cys5 and Cys10 residues involved in the disulfide bridge, and the Phe6, Lys8 and Tyr9 residues. Free alpha-amino group and C-terminal COOH group are not necessary for the biological activity, and modifications of these radicals may even increase the stability of the analogs. Punctual substitution of native amino acids, notably Phe6 and Trp7, by particular residues generates analogs with antagonistic properties. These studies, which provide crucial information regarding the structural and conformational requirements for ligand-receptor interactions, will be of considerable importance for the design of novel UT ligands with increased selectivity, potency and stability, that may eventually lead to the development of innovative drugs.

Published
2008
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50. Reciprocal Regulation of Plasma Apelin and Vasopressin by Osmotic Stimuli

Author

Xavier Iturrioz, Séverine Peyrard, Anne Blanchard, Nicolas Chartrel, Nadia De Mota, Hubert Vaudry, Catherine Llorens-Cortes, Pierre Corvol, Michel Azizi, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CIC AP-HP (hegp Ex-Broussais)/inserm, Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropeptides centraux et régulations hydrique et cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), Labex MemoLife, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathologie vasculaire et endocrinologie rénale - Chaire de médecine expérimentale (INSERM U36), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM), Iturrioz, Xavier, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre interdisciplinaire de recherche en biologie (CIRB), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Labex MemoLife, Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Llorens Cortes, Catherine

Subjects
Male, Vasopressin, MESH: Renin, [SDV]Life Sciences [q-bio], MESH: Saline Solution, Hypertonic, MESH: Arginine Vasopressin, MESH: Body Fluids, Electrolytes, MESH: Osmolar Concentration, 0302 clinical medicine, MESH: Electrolytes, Renin, [CHIM] Chemical Sciences, Blood plasma, MESH: Blood Proteins, Homeostasis, ComputingMilieux_MISCELLANEOUS, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 0303 health sciences, Chemistry, Blood Proteins, General Medicine, Water-Electrolyte Balance, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Body Fluids, Apelin, [SDV] Life Sciences [q-bio], Hematocrit, MESH: Homeostasis, Nephrology, Intercellular Signaling Peptides and Proteins, MESH: Drinking, hormones, hormone substitutes, and hormone antagonists, Adult, medicine.medical_specialty, Adolescent, Drinking, MESH: Hematocrit, 03 medical and health sciences, Clinical Research, Osmotic Pressure, Internal medicine, Renin–angiotensin system, medicine, Humans, [CHIM]Chemical Sciences, MESH: Intercellular Signaling Peptides and Proteins, 030304 developmental biology, Saline Solution, Hypertonic, MESH: Adolescent, MESH: Humans, Osmolar Concentration, MESH: Adult, MESH: Osmotic Pressure, MESH: Male, Hypertonic saline, Arginine Vasopressin, Plasma osmolality, Endocrinology, nervous system, MESH: Water-Electrolyte Balance, Magnocellular cell, 030217 neurology & neurosurgery
Abstract

International audience; Apelin is a neuropeptide that co-localizes with vasopressin (AVP) in magnocellular neurons and is involved in body fluid homeostasis. Osmotic stimuli have opposite effects on the regulation of apelin and AVP secretion in animal models, but whether this is true in humans is unknown. This study investigated the relationship among osmolality, apelin, and AVP in 10 healthy men after infusion of hypertonic saline or loading with water to increase and decrease plasma osmolality, respectively. Increasing plasma osmolality was accompanied by a parallel, linear increase in plasma AVP concentration and by a decrease in plasma apelin concentration. In contrast, decreasing plasma osmolality by water loading reduced plasma AVP concentration and rapidly increased plasma apelin concentration. These findings suggest that regulation of apelin secretion contributes to the maintenance of body fluid homeostasis.

Published
2008
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