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131 results on '"Coppola, Thierry"'

1. Bridging the Gap Between Diabetes and Stroke in Search of High Clinical Relevance Therapeutic Targets

Author

Coppola, Thierry, Béraud-Dufour, Sophie, Lebrun, Patricia, and Blondeau, Nicolas

Subjects
Quantitative Biology - Tissues and Organs, Quantitative Biology - Neurons and Cognition
Abstract

Diabetes affects more than 425 million people worldwide, a scale approaching pandemic proportion. Diabetes represents a major risk factor for stroke, and therefore is actively addressed for stroke prevention. However, how diabetes affects stroke severity has not yet been extensively considered, which is surprising given the evident but understudied common mechanistic features of both pathologies. The increase in number of diabetic people, in the incidence of stroke in presence of this specific risk factor, and the exacerbation of ischemic brain damage in diabetic conditions (at least in animal models) warrant the need to integrate this comorbidity in pre-clinical studies of brain ischemia to develop novel therapeutic approaches. Therefore, a better understanding of the commonalties involved in the course of both diseases would offer the promise of discovering novel neuroprotective pathways that would be more appropriated to clinical situations. In this article, we will review the relevant mechanisms that have been identified as common traits of both pathologies and that could be to our knowledge, potential targets for both pathologies., Comment: NeuroMolecular Medicine, Humana Press, 2019

Published
2020
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5. Unlocking Therapeutic Synergy: Tailoring Drugs for Comorbidities such as Depression and Diabetes through Identical Molecular Targets in Different Cell Types.

Author

Coppola, Thierry, Daziano, Guillaume, Legroux, Ilona, Béraud-Dufour, Sophie, Blondeau, Nicolas, and Lebrun, Patricia

Subjects
*DRUG target, *DRUG synergism, *SEROTONIN uptake inhibitors, *COMORBIDITY, *ANTIDEPRESSANTS, *SEROTONIN, *AFFECTIVE disorders, *LUTEINIZING hormone releasing hormone
Abstract

Research in the field of pharmacology aims to generate new treatments for pathologies. Nowadays, there are an increased number of chronic disorders that severely and durably handicap many patients. Among the most widespread pathologies, obesity, which is often associated with diabetes, is constantly increasing in incidence, and in parallel, neurodegenerative and mood disorders are increasingly affecting many people. For years, these pathologies have been so frequently observed in the population in a concomitant way that they are considered as comorbidities. In fact, common mechanisms are certainly at work in the etiology of these pathologies. The main purpose of this review is to show the value of anticipating the effect of baseline treatment of a condition on its comorbidity in order to obtain concomitant positive actions. One of the implications would be that by understanding and targeting shared molecular mechanisms underlying these conditions, it may be possible to tailor drugs that address both simultaneously. To this end, we firstly remind readers of the close link existing between depression and diabetes and secondly address the potential benefit of the pleiotropic actions of two major active molecules used to treat central and peripheral disorders, first a serotonin reuptake inhibitor (Prozac ®) and then GLP-1R agonists. In the second part, by discussing the therapeutic potential of new experimental antidepressant molecules, we will support the concept that a better understanding of the intracellular signaling pathways targeted by pharmacological agents could lead to future synergistic treatments targeting solely positive effects for comorbidities. [ABSTRACT FROM AUTHOR]

Published
2023
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12. Expression cloning of a protective Leishmania antigen

Author

Mougneau, Evelyne, Altare, Frederic, Wakil, Adil E., Zheng, Shichun, Coppola, Thierry, Wang, Zhi-En, Waldmann, Rainer, Locksley, Richard M., and Glaichenhaus, Nicolas

Subjects
Immune response -- Physiological aspects, CD4 lymphocytes -- Physiological aspects, Leishmaniasis -- Prevention, Science and technology, Prevention, Physiological aspects
Abstract

Parasite-specific CD4+ T cells have-been shown to transfer protection against Leishmania major in susceptible BALB/c mice. An epitope-tagged expression library was used to identify the antigen recognized by a protective CD4+ T cell clone. The expression library allowed recombinant proteins made in bacteria to be captured by macrophages for presentation to T cells restricted to major histocompatibility complex class II. A conserved 36-kilodalton member of the tryptophan-aspartic acid repeat family of proteins was identified that was expressed in both stages of the parasite life cycle. A 24-kilodalton portion of this antigen protected susceptible mice when administered as a vaccine with interleukin-12 before infection., The immunology of Leishmania major infection has been characterized in inbred strains of mice. The response is CD4-dependent, presumably reflecting the residence of the obligate intracellular amastigotes in macrophages within [...]

Published
1995

15. Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin

Author

Hivelin, Céline, Béraud-Dufour, Sophie, Devader, Christelle, Abderrahmani, Amar, Moreno, Sébastien, Moha ou Maati, Hamid, Djillani, Alaeddine, Heurteaux, Catherine, Borsotto, Marc, Mazella, Jean, Coppola, Thierry, Institut de pharmacologie moléculaire et cellulaire (IPMC), 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), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), 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 National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle (IGF), 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), This work was supported by the Centre National de la Recherche Scientifique, a grant from the Société Francophone du Diabète (SFD 2011) to Thierry Coppola and a grant from the Agence Nationale de la Recherche (ANR-13-SAMA-0002) to Jean Mazella. Amar Abderrahmani is supported by 'European Genomic Institute for Diabetes' (EGID, ANR-10-LABX-46), European Commission, the Regional Council Nord Pas de Calais and the European Regional Development Fund. Alaeddine Djillani is supported by ICST LabEx., ANR-13-SAMA-0002,VASPAC,Validation du concept spadine pour le traitement de la dépression(2013), ANR-10-LABX-0046,EGID,EGID Diabetes Pole(2010), ANR-11-LABX-0015,ICST,Canaux ioniques d'intérêt thérapeutique(2011), Béraud-Dufour, Sophie, Santé Mentale et Addictions - Validation du concept spadine pour le traitement de la dépression - - VASPAC2013 - ANR-13-SAMA-0002 - SAMENTA - VALID, EGID Diabetes Pole - - EGID2010 - ANR-10-LABX-0046 - LABX - VALID, Laboratoires d'excellence - Canaux ioniques d'intérêt thérapeutique - - ICST2011 - ANR-11-LABX-0015 - LABX - VALID, 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), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, endocrine system, lcsh:RC648-665, Article Subject, [SDV]Life Sciences [q-bio], lcsh:Diseases of the endocrine glands. Clinical endocrinology, Cell Line, Membrane Potentials, [SDV] Life Sciences [q-bio], Islets of Langerhans, Mice, Cytosol, Glucose, Potassium Channels, Tandem Pore Domain, Insulin-Secreting Cells, Insulin Secretion, Animals, Insulin, Calcium, Peptides, Research Article
Abstract

International audience; Inhibition of the potassium channels TREK-1 by spadin (SPA) is currently thought to be a promising therapeutic target for the treatment of depression. Since these channels are expressed in pancreatic β-cells, we investigated their role in the control of insulin secretion and glucose homeostasis. In this study, we confirmed the expression of TREK-1 channels in the insulin secreting MIN6-B1 β-cell line and in mouse islets. We found that their blockade by SPA potentiated insulin secretion induced by potassium chloride dependent membrane depolarization. Inhibition of TREK-1 by SPA induced a decrease of the resting membrane potential ( mV) and increased the cytosolic calcium concentration. In mice, administration of SPA enhanced the plasma insulin level stimulated by glucose, confirming its secretagogue effect observed in vitro. Taken together, this work identifies SPA as a novel potential pharmacological agent able to control insulin secretion and glucose homeostasis.

Published
2016

18. Potentiation of Calcium Influx and Insulin Secretion in Pancreatic Beta Cell by the Specific TREK-1 Blocker Spadin

Author

Hivelin, Céline, primary, Béraud-Dufour, Sophie, additional, Devader, Christelle, additional, Abderrahmani, Amar, additional, Moreno, Sébastien, additional, Moha ou Maati, Hamid, additional, Djillani, Alaeddine, additional, Heurteaux, Catherine, additional, Borsotto, Marc, additional, Mazella, Jean, additional, and Coppola, Thierry, additional

Published
2016
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26. Spadin, a Sortilin-Derived Peptide, Targeting Rodent TREK-1 Channels: A New Concept in the Antidepressant Drug Design

Author

Mazella, Jean, primary, Pétrault, Olivier, additional, Lucas, Guillaume, additional, Deval, Emmanuel, additional, Béraud-Dufour, Sophie, additional, Gandin, Carine, additional, El-Yacoubi, Malika, additional, Widmann, Catherine, additional, Guyon, Alice, additional, Chevet, Eric, additional, Taouji, Said, additional, Conductier, Grégory, additional, Corinus, Alain, additional, Coppola, Thierry, additional, Gobbi, Gabriella, additional, Nahon, Jean-Louis, additional, Heurteaux, Catherine, additional, and Borsotto, Marc, additional

Published
2010
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36. VAMP2, but Not VAMP3/Cellubrevin, Mediates Insulin-dependent Incorporation of GLUT4 into the Plasma Membrane of L6 Myoblasts

Author

Randhawa, Varinder K., primary, Bilan, Philip J., additional, Khayat, Zayna A., additional, Daneman, Nicholas, additional, Liu, Zhi, additional, Ramlal, Toolsie, additional, Volchuk, Allen, additional, Peng, Xiao-Rong, additional, Coppola, Thierry, additional, Regazzi, Romano, additional, Trimble, William S., additional, and Klip, Amira, additional

Published
2000
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42. The calcium channel antagonists receptor from rabbit skeletal muscle.

Author

Barhanin, Jacques, Coppola, Thierry, Schmid, Annie, Borsotto, Marc, and Lazdunski, Michel

Subjects
*CALCIUM antagonists, *CARDIOVASCULAR agents, *CALCIUM channels, *ION channels, *MUSCLES, *RABBITS
Abstract

The Ca2+ channel antagonists receptor from rabbit skeletal muscle was purified to homogeneity. Following reconstitution into phosphatidylcholine vesicles, binding experiments with (+)[³H]PN 200-110, (-)[³H]D888 and d-cis-[³H]diltiazem demonstrated that receptor sites for the three most common Ca2+ channel markers copurified with binding stoichiometries close to 1:1:1. Sodium dodecyl sulfate gel analysis of the purified receptor showed that it is composed of only one protein of Mr 170 000 under non-reducing conditions and of two polypeptides of Mr 140 000 and 32 000 under disulfide reducing conditions. Iodination of the protein of Mr 170 000 and immunoblots experiments with antisera directed against the differents components demonstrated that the Ca2+ channel antagonists receptor is a complex of Mr 170 000 composed of a polypeptide chain of Mr 140 000 associated to one polypeptide chain of Mr 32 000 by disulfide bridges. One of the problems concerning this subunit structure of the putative Ca2+ channel was the presence of smaller polypeptide chains of Mr 29 000 and 25 000. Peptide mapping of these polypeptide chains and analysis of their cross-reactivity with sera directed against the proteins of Mr 170 000 and 32 000 demonstrated that they were degradative products of the Mr 32 000 component. Both the large (140 kDa) and the small (32 kDa) component of the putative Ca2+ channel are heavily glycosylated. At least 20-22% of their mass were removed by enzymatic deglycosylation. Finally the possibility that both the 140-kDa and 32-kDa components originate from a single polypeptide chain of Mr 170 000 which is cleaved by proteolysis upon purification is discussed. [ABSTRACT FROM AUTHOR]

Published
1987
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44. High affinity Rab3 binding is dispensable for Rabphilin-dependent potentiation of stimulated secretion

Author

Joberty, Gérard, Stabila, Paul F., Coppola, Thierry, Macara, Ian G., and Regazzi, Romano

Abstract

Rabphilin is a protein that associates with the GTP-bound form of Rab3, a small GTPase that controls a late step in Ca2+-triggered exocytosis. Rabphilin is found only in neuroendocrine cells where it co-localises with Rab3A on the secretory vesicle membrane. The Rab3 binding domain (residues 45 to 170), located in the N-terminal part of Rabphilin, includes a cysteine-rich region with two zinc finger motifs that are required for efficient interaction with the small GTPase. To determine whether binding to Rab3A is necessary for the subcellular localisation of Rabphilin, we synthesised point mutants within the Rab3-binding domain. We found that two unique mutations (V61A and L83A) within an amphipathic α-helix of this region abolish detectable binding to endogenous Rab3, but only partially impair the targetting of the protein to secretory vesicles in PC12 and pancreatic HIT-T15 cells. Furthermore, both mutants transfected in the HIT-T15 beta cell line stimulate Ca2+-regulated exocytosis to the same extent as wild-type Rabphilin. Surprisingly, another Rabphilin mutant, R60A, which possesses a wild-type affinity for Rab3, and targets efficiently to membranes, does not potentiate regulated secretion. High affinity binding to Rab3 is therefore dispensable for the targetting of Rabphilin to secretory vesicles and for the potentiation of Ca2+-regulated secretion. The effects of Rabphilin on secretion may be mediated through interaction with another, unknown, factor that recognizes the Rab3 binding domain.

Published
1999
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45. Cloning provides evidence for a family of inward rectifier and G‐protein coupled K+channels in the brain

Author

Lesage, Florian, Duprat, Fabrice, Fink, Michel, Guillemare, Eric, Coppola, Thierry, Lazdunski, Michel, and Hugnot, Jean-Philippe

Abstract

MbIRK3, mbGIRK2 and mbGIRK3 K+channels cDNAs have been cloned from adult mouse brain. These eDNAs encode polypeptides of 445, 414 and 376 amino acids, respectively, which display the hallmarks of inward rectifier K+channels, i.e. two hydrophobic membrane‐spanning domains M1 and M2 and a pore‐forming domain H5. MbIRK3 shows around 65% amino acid identity with IRK1 and rbIRK2 and only 50% with ROMK1 and GIRK1. On the other hand, mbGIRK2 and mbGIRK3 are more similar to GIRK1 (60%) than to ROMK1 and IRK1 (50%). Northern blot analysis reveals that these three novel clones are mainly expressed in the brain. Xenopusoocytes injected with mbIRK3 and mbGIRK2 cRNAs display inward rectifier K+‐selective currents very similar to IRK1 and GIRK1, respectively. As expected from the sequence homology, mbGIRK2 cRNA directs the expression of G‐protein coupled inward rectifyer K+channels which has been observed through their functional coupling with co‐expressed δ‐opioid receptors. These results provide the first evidence that the GIRK family, as the IRK family, is composed of multiple genes with members specifically expressed in the nervous system.

Published
1994
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46. Molecular Properties of Structure and Regulation of the Calcium Channela

Author

LAZDUNSKI, MICHEL, primary, BARHANIN, JACQUES, additional, BORSOTTO, MARC, additional, COGNARD, CHRISTIAN, additional, COOPER, CHRISTIE, additional, COPPOLA, THIERRY, additional, FOSSET, MICHEL, additional, GALIZZI, JEAN‐PIERRE, additional, HOSEY, MARLENE M., additional, MOURRE, CHRISTIANE, additional, RENAUD, JEAN‐FRANCOIS, additional, ROMEY, GEORGES, additional, SCHMID, ANNIE, additional, and VANDAELE, SYLVIE, additional

Published
1988
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49. Neurotensin receptor-2 and -3 are crucial for the anti-apoptotic effect of neurotensin on pancreatic beta-TC3 cells.

Author

Béraud-Dufour S, Coppola T, Massa F, and Mazella J

Subjects
Animals, Caspase 3 metabolism, Cell Line, Cytoprotection, Insulin-Secreting Cells immunology, Insulin-Secreting Cells pathology, Mice, Neurotensin immunology, Phosphatidylinositol 3-Kinases metabolism, Protein Binding, Protein Transport, RNA, Small Interfering genetics, Receptors, Neurotensin genetics, Receptors, Neurotensin immunology, Signal Transduction, Staurosporine metabolism, Apoptosis immunology, Insulin-Secreting Cells metabolism, Neurotensin metabolism, Receptors, Neurotensin metabolism
Abstract

The neuropeptide neurotensin (NT) has been recently shown to protect pancreatic beta cells from toxic agents-induced apoptosis through interaction with the NT receptor-2 (NTSR2) and activation of the phosphatidylinositol-3 kinase pathway. However, expression of the NT receptor-3/sortilin (NTSR3) in the mouse pancreatic beta cell line -TC3 led us to investigate its possible functional role in these cells. By using siRNA, immunoprecipitation, co-localization and caspase-3 assays,we provide evidence for a functional endogenous interaction between NTSR2 and NTSR3. Expression of both receptors is necessary for the protective action of NT on staurosporine-induced caspase-3 activity in -TC3 cells. Moreover, NTSR2 and NTSR3 co-immunoprecipitate and are co-localized at the plasma membrane. Thus, the NT response in beta cells is controlled by the formation of a functional complex between NTSR2 and NTSR3.

Published
2009
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50. Functional assays for the investigation of the role of Rab GTPase effectors in dense core granule release.

Author

Cheviet S, Coppola T, and Regazzi R

Subjects
Animals, Base Sequence, Blotting, Western, Cell Line, Cytoplasmic Granules enzymology, Exocytosis, Molecular Sequence Data, RNA Interference, Subcellular Fractions enzymology, rab GTP-Binding Proteins metabolism
Abstract

Rab3 and Rab27 GTPases control late events in the secretory pathway of mammalian cells including docking and fusion of secretory vesicles with the plasma membrane. The action of Rab3 and Rab27 on the exocytotic process is exerted through the activation of specific effectors. Several proteins with the capacity to interact in a GTP-dependent manner with Rab3 and Rab27 have been identified. However, for most of these potential Rab effectors a precise function in the secretory process has not yet been attributed. In this chapter we describe a series of approaches that can be applied to assess the properties of Rab3 and Rab27 effectors and their potential role in the regulation of dense core granule release.

Published
2005
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