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1. In primary effusion lymphoma cells, MYB transcriptional repression is associated with v-FLIP expression during latent KSHV infection while both v-FLIP and v-GPCR become involved during the lytic cycle

Author

Françoise Valensi, Antoine Gessain, Christophe Nicot, Hittu Matta, Renaud Mahieux, Preet M. Chaudhary, Vincent Lacoste, Jean Gabarre, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Department of Microbiology, Molecular genetics and Immunology, University of Kansas Medical Center [Lawrence], Laboratory of molecular mechanisms of hematologic disorders and therapeutic implications (ERL 8254 - Equipe Inserm U1163), Imagine - Institut des maladies génétiques (IMAGINE - U1163), 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), Service d'Hématologie Clinique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Division of Hematology-Oncology and the Hillman Cancer Center, University of Pittsburgh Medical Center, This work was supported by a grant from l'Association de Recherche sur le Cancer (ARC) and from la Fondation de France to RM and grants from NIH (CA85177 and CA124621) to PMC. VL and CN were supported by a bourse Pasteur‐Weissman and la Ligue Nationale Contre le Cancer respectively. RM was supported by a bourse Roux, from the Institut Pasteur and by INSERM., We thank Dr D. Gonzalez‐Dunia, J.S. Seeler and C. Royer‐Leveau for their help. We are indebted to Drs P. Charneau, J. Golay, N. Rice, L. Boxer, P. Murphy and W.C. Greene for generous gifts of reagents essential to the realization of this study. We thank Pr O. Hermine for providing us with some PEL fresh samples, and Dr Timothy Stinear for his critical comments., Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Kansas Medical Center [Kansas City, KS, USA], Université Paris Descartes - Paris 5 (UPD5)-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), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), Service d'Hématologie clinique [CHU Pitié-Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), University of Kansas Medical Center, Laboratoire d'hématologie ( ERL 8254 ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), 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 ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]

Subjects
non-Hodgkinlymphoma, Transcription, Genetic, Genes, myb, [SDV]Life Sciences [q-bio], viruses, CASP8 and FADD-Like Apoptosis Regulating Protein, Gene Expression, MESH : Sarcoma, Kaposi, MESH : Herpesvirus 8, Human, MESH: Virus Activation, Receptors, G-Protein-Coupled, Transduction (genetics), molecular studies, 0302 clinical medicine, MESH: Lymphoma, Non-Hodgkin/virology, Transduction, Genetic, MESH: Viral Proteins/metabolism, Virus latency, MESH : Virus Latency, MYB, MESH : Cell Transformation, Viral, Viral G-Protein Coupled Receptor, MESH : Viral Proteins, MESH: Lymphoma, AIDS-Related/metabolism, Lymphoma, AIDS-Related, Regulation of gene expression, MESH : Trans-Activators, 0303 health sciences, Lymphoma, Non-Hodgkin, MESH: Virus Latency, NF-kappa B, Hematology, Transfection, MESH : Immediate-Early Proteins, MESH: Transduction, Genetic, MESH: Gene Expression Regulation, Viral, MESH: Sarcoma, Kaposi/metabolism, MESH: Herpesvirus 8, Human/physiology, Virus Latency, 3. Good health, Lytic cycle, MESH: Cell Transformation, Viral, MESH : NF-kappa B, MESH : Genes, myb, 030220 oncology & carcinogenesis, Herpesvirus 8, Human, MESH : Virus Activation, MESH : Receptors, G-Protein-Coupled, Primary effusion lymphoma, MESH : Transfection, MESH: NF-kappa B/metabolism, Gene Expression Regulation, Viral, MESH: Cell Line, Tumor, MESH: Gene Expression, animal structures, MESH : Transduction, Genetic, MESH : Lymphoma, AIDS-Related, Biology, MESH : Gene Expression Regulation, Viral, Immediate-Early Proteins, Proto-Oncogene Proteins c-myb, Viral Proteins, 03 medical and health sciences, MESH: Receptors, G-Protein-Coupled/metabolism, MESH: Sarcoma, Kaposi/virology, MESH: Trans-Activators/metabolism, Cell Line, Tumor, medicine, nuclear factor-jB, Humans, MESH : Lymphoma, Non-Hodgkin, MESH: CASP8 and FADD-Like Apoptosis Regulating Protein/metabolism, Sarcoma, Kaposi, 030304 developmental biology, B cells, MESH: Humans, MESH : Cell Line, Tumor, herpes virus, MESH: Lymphoma, AIDS-Related/virology, MESH: Transcription, Genetic, MESH: Transfection, MESH: Immediate-Early Proteins/metabolism, MESH : Humans, MESH: Proto-Oncogene Proteins c-myb/analysis, MESH : Transcription, Genetic, Kaposi sarcoma, MESH : CASP8 and FADD-Like Apoptosis Regulating Protein, Cell Transformation, Viral, medicine.disease, MESH : Proto-Oncogene Proteins c-myb, MESH : Gene Expression, MESH: Genes, myb, Trans-Activators, Cancer research, MESH: Lymphoma, Non-Hodgkin/metabolism, Virus Activation
Abstract

International audience; Primary effusion lymphoma (PEL) is a rare, distinct subtype of non-Hodgkin lymphoma, which is associated with Kaposi sarcoma-associated herpesvirus (KSHV) infection. Although MYB levels are high in most neoplastic B cells, we found that, unexpectedly, both PEL cells and uncultured PEL patients' samples contained very low levels of MYB mRNA when compared to B-cell leukaemia samples obtained from KSHV(-) patients. These results were further confirmed at the protein level. Both latent viral FLICE inhibitory protein (v-FLIP) and early lytic viral G protein coupled receptor (v-GPCR) KSHV proteins were found to activate nuclear factor (NF)-kappaB and transrepress a MYB promoter reporter construct. In contrast, a dominant negative inhibitor of NF-kappaB (IkappaB-alpha) mutant prevented v-FLIP and v-GPCR from inhibiting MYB functions while a v-GPCR mutant that was impaired for NF-kappaB activation could not repress the MYB construct. Transduction of a v-FLIP expressing vector or stable transfection of v-GPCR both resulted in a marked downregulation of the endogenous MYB protein expression. However, MYB expression transactivated the lytic switch Replication and Transcription Activator (RTA) promoter in transient transfection assays. Taken together, our results demonstrate that, contrary to a number of other haematological malignancies, MYB expression is not required for PEL cell proliferation. Repressing MYB expression also helps in maintaining the virus in latency.

Published
2007
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2. Human genetic polymorphisms in T1R1 and T1R3 taste receptor subunits affect their function

Author

Claire Schlegel-Le-Poupon, Annick Faurion, Jean-Claude Pernollet, Singh Preet Bano, Christine Belloir, Hélène Débat, Loïc Briand, Brice Hoffmann, Anna Wiencis, Maud Sigoillot, Claude Nespoulous, Marta Grauso, Jean-Pierre Montmayeur, Mariam Raliou, Didier Trotier, Briand, Loïc, Neurobiologie de l'Olfaction et de la Prise Alimentaire - Biochimie de l'Olfaction et de la Gustation, Institut National de la Recherche Agronomique (INRA), 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), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Institut de Neurobiologie Alfred Fessard (INAF), Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique ( INRA ), 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 ), Université Versailles St-Quentin, Institut de Neurobiologie Alfred Fessard ( INAF ), Centre National de la Recherche Scientifique ( CNRS ), and Neurobiologie de l'Olfaction et de la Prise Alimentaire (NOPA)

Subjects
Nonsynonymous substitution, Models, Molecular, Taste, 030309 nutrition & dietetics, Physiology, Monosodium glutamate, MESH : Polymorphism, Genetic, saccharin, MESH : Immunohistochemistry, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, récepteur gustatif, goût, Umami, MESH : Blotting, Western, MESH: Receptors, G-Protein-Coupled, perception, gustation, Receptors, G-Protein-Coupled, Behavioral Neuroscience, chemistry.chemical_compound, MESH : Taste Threshold, Taste receptor, taste receptor, Sodium Glutamate, structure cristalline, dynamique moléculaire, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, papillae, Cells, Cultured, Genetics, 0303 health sciences, molecular dynamic, MESH: Taste Threshold, mammifère, récepteur couplé aux protéines G, MESH: Amino Acid Substitution, umami, Immunohistochemistry, Sensory Systems, Transmembrane domain, Biochemistry, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Alimentation et Nutrition, Taste Threshold, récepteur glutamate, MESH : Receptors, G-Protein-Coupled, MESH: Models, Molecular, MESH: Cells, Cultured, t1r3, crystal structure, t1r1, MESH : Sodium Glutamate, MESH : Models, Molecular, Blotting, Western, différence individuelle, G protein coupled receptor, glutamate, individual difference, mammalian sweet, 03 medical and health sciences, protein coupled receptor, MESH : Amino Acid Substitution, man, Physiology (medical), MESH : Cells, Cultured, MESH: Polymorphism, Genetic, saccharine, MESH: Blotting, Western, Food and Nutrition, Humans, mammals, l glutamate, human, metabotropic glutamate receptor, umami taste, 030304 developmental biology, G protein-coupled receptor, MESH: Humans, Polymorphism, Genetic, papilla, MESH: Sodium Glutamate, MESH : Humans, snp, MESH: Immunohistochemistry, gustatory receptor, molecular dynamics, chemistry, crystalline structure, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Amino Acid Substitution, Metabotropic glutamate receptor, msg, saccharin preference, humain, papille
Abstract

International audience; Umami is the typical taste induced by monosodium glutamate (MSG), which is thought to be detected by the heterodimeric G protein-coupled receptor, T1R1 and T1R3. Previously, we showed that MSG detection thresholds differ substantially between individuals and we further showed that nontaster and hypotaster subjects are associated with nonsynonymous single polymorphisms occurring in the T1R1 and T1R3 genes. Here, we show using functional expression that both amino acid substitutions (A110V and R507Q) in the N-terminal ligand-binding domain of T1R1 and the 2 other ones (F749S and R757C), located in the transmembrane domain of T1R3, severely impair in vitro T1R1/T1R3 response to MSG. A molecular model of the ligand-binding region of T1R1/T1R3 provides a mechanistic explanation supporting functional expression data. The data presented here support causal relations between the genotype and previous in vivo psychophysical studies in human evaluating sensitivity to MSG.

Published
2011
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3. Jacques Benoit lecture: the neuroendocrine view of the angiotensin and apelin systems

Author

Claude Kordon, Catherine Llorens-Cortes, Neuropeptides centraux et régulations hydrique et cardiovasculaire, 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), 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)-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), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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 Pierre et Marie Curie - Paris 6 (UPMC)-Centre interdisciplinaire de recherche en biologie (CIRB), École normale supérieure - Paris (ENS-PSL), 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), Llorens Cortes, Catherine, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Collège de France ( CdF ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR Necker-Enfants Malades ( IRNEM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH : Glutamyl Aminopeptidase, MESH: Signal Transduction, Angiotensin receptor, Vasopressin, Endocrinology, Diabetes and Metabolism, MESH : Models, Biological, MESH: Receptors, G-Protein-Coupled, MESH : Tissue Distribution, 0302 clinical medicine, Endocrinology, MESH: Renin-Angiotensin System, MESH: Animals, Receptor, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, MESH: Glutamyl Aminopeptidase, 0303 health sciences, MESH : Rats, MESH: Blood Pressure, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, 3. Good health, Apelin, MESH: Enzyme Inhibitors, MESH : Receptors, G-Protein-Coupled, hormones, hormone substitutes, and hormone antagonists, MESH : Angiotensins, medicine.medical_specialty, MESH: Rats, Neuropeptide, Biology, MESH: Cardiovascular Physiological Phenomena, 03 medical and health sciences, Cellular and Molecular Neuroscience, MESH: Brain, Internal medicine, Renin–angiotensin system, MESH : Blood Pressure, medicine, MESH: Tissue Distribution, MESH: Intercellular Signaling Peptides and Proteins, MESH : Intercellular Signaling Peptides and Proteins, 030304 developmental biology, Apelin receptor, MESH : Signal Transduction, MESH : Enzyme Inhibitors, MESH: Angiotensins, MESH: Humans, MESH : Water-Electrolyte Balance, MESH : Cardiovascular Physiological Phenomena, Endocrine and Autonomic Systems, MESH : Humans, MESH: Models, Biological, MESH : Brain, MESH: Neurosecretory Systems, MESH: Water-Electrolyte Balance, MESH : Animals, MESH : Neurosecretory Systems, MESH : Renin-Angiotensin System, 030217 neurology & neurosurgery, Homeostasis
Abstract

International audience; The hyperactivity of the brain renin-angiotensin system (RAS) has been implicated in the development and maintenance of hypertension in several types of experimental and genetic hypertension animal models. Among the main bioactive peptides of the brain RAS, angiotensin (Ang) II and Ang III display the same affinity for type 1 and type 2 Ang II receptors. Both peptides, injected intracerebroventricularly, similarly increase arginine vasopressin (AVP) release and blood pressure (BP); however, because Ang II is converted in vivo to Ang III, the identity of the true effector is unknown. We review new insights into the predominant role of brain Ang III in the control of BP, underlining the fact that brain aminopeptidase A (APA), the enzyme generating brain Ang III, may therefore be an interesting candidate target for the treatment of hypertension. This justifies the development of potent systemically active APA inhibitors, such as RB150, as prototypes of a new class of antihypertensive agents for the treatment of certain forms of hypertension. We also searched for a putative angiotensin receptor subtype specific for Ang III and isolated a seven transmembrane-domain G protein-coupled receptor corresponding to the receptor for apelin, a newly-discovered peptide isolated from bovine stomach. Apelin and its receptor are expressed in magnocellular vasopressinergic neurones in the hypothalamus. The central injection of apelin in lactating rats decreases the phasic electrical activity of vasopressinergic neurones and the systemic secretion of AVP, inducing water diuresis. Apelin is therefore a natural inhibitor of the antidiuretic effect of AVP. In addition, systemic administration of apelin decreases BP, improves cardiac contractility and reduces cardiac loading. The development of nonpeptide agonists of the apelin receptor may provide new therapeutic tools for treating water retention, hyponatraemia and cardiovascular diseases. Angiotensins and apelin thus exert opposing but complementary effects, and are thereby determinant for the maintenance of body fluid homeostasis and cardiovascular functions.

Published
2008
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4. Genetic study of the melanin-concentrating hormone receptor 2 in childhood and adulthood severe obesity

Author

Chantal Samson, Christophe Wachter, Claire Levy-Marchal, Maïté Tauber, Serge Hercberg, Barbara Heude, Catherine Le Stunff, Philippe Froguel, Victor Abkevich, Cécile Lecoeur, Maya Ghoussaini, Jacques Weill, Pierre Bougnères, David Meyre, Patrick Tounian, Vincent Vatin, Adib Younus, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Myriad Genetics Inc, Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pediatric Endocrine Unit, Hôpital Jeanne de Flandre [Lille], Pancréas endocrine et diabète de l'enfant, Institut National de la Santé et de la Recherche Médicale (INSERM), Immunologie, génétique et traitement des maladies métaboliques et du diabète (UMR_S 561), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Genomic Medicine, Imperial College London-Hammersmith Hospital, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de gastro-entérologie [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Génétique des maladies multifactorielles ( GMM ), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique ( CNRS ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de gastro-entérologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Unité de Recherche en Epidémiologie Nutritionnelle ( UREN ), Université Paris 13 ( UP13 ) -Institut National de la Recherche Agronomique ( INRA ) -Conservatoire National des Arts et Métiers [CNAM] ( CNAM ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Immunologie, génétique et traitement des maladies métaboliques et du diabète ( UMR_S 561 ), and Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 )

Subjects
Male, MESH : Molecular Sequence Data, Genetic Linkage, Endocrinology, Diabetes and Metabolism, Eating Disorders, Clinical Biochemistry, Appetite, MESH: DNA Replication, MESH: Receptors, G-Protein-Coupled, MESH: Amino Acid Sequence, Biochemistry, Receptors, G-Protein-Coupled, Body Mass Index, Cohort Studies, MESH : Exons, 0302 clinical medicine, Endocrinology, MESH : Child, MESH: Child, Receptors, MESH: Obesity, MESH : Female, Child, MESH: Cohort Studies, 2. Zero hunger, 0303 health sciences, Pituitary Hormone, MESH : Amino Acid Sequence, Linkage (Genetics), [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Receptors, Pituitary Hormone, MESH : Feeding Behavior, Exons, MESH : Adult, MESH : Receptors, Pituitary Hormone, MESH : Eating Disorders, Hormone receptor, MESH: Feeding Behavior, MESH : Obesity, MESH : Receptors, G-Protein-Coupled, Female, MESH: Eating Disorders, MESH : DNA Replication, MESH : Appetite, Adult, DNA Replication, medicine.medical_specialty, MESH : Male, Molecular Sequence Data, MESH : Cohort Studies, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Context (language use), Biology, Childhood obesity, MESH: Body Mass Index, Feeding and Eating Disorders, 03 medical and health sciences, G-Protein-Coupled, Internal medicine, medicine, SNP, Humans, Receptors, Pituitary Hormone, Obesity, Amino Acid Sequence, MESH : Haplotypes, Alleles, 030304 developmental biology, MESH: Humans, MESH: Molecular Sequence Data, MESH: Alleles, MESH : Humans, Biochemistry (medical), MESH: Adult, Odds ratio, Feeding Behavior, MESH: Haplotypes, medicine.disease, MESH: Male, Melanin-concentrating hormone receptor, MESH : Body Mass Index, Haplotypes, MESH: Appetite, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Alleles, MESH: Exons, MESH: Female, MESH: Linkage (Genetics), MESH : Linkage (Genetics)
Abstract

http://jcem.endojournals.org/cgi/rapidpdf/jc.2006-2316v1; International audience; CONTEXT: The melanin-concentrating hormone receptor 2 (MCHR2) is a G protein-coupled receptor for melanin-concentrating hormone, a neuropeptide that plays an important role in feeding behaviors. MCHR2 maps on chromosome 6q16.3, in a susceptibility locus for childhood obesity. OBJECTIVE: The aim of this study was to investigate the association between MCHR2 variation and human obesity. DESIGN: Case control and family-based studies were performed. PARTICIPANTS: A total of 141 obese children and 24 nonobese adult subjects was sequenced, and case-control analyses were conducted using 628 severely obese children and 1,401 controls. RESULTS: There were 11 single nucleotide polymorphisms (SNPs) identified. We showed nominal association among -38,245 ATG A/G SNP (P = 0.03; 95% confidence interval 1.02-1.34; odds ratio 1.17), A76A T/C SNP (P = 0.03; 95% confidence interval 0.58-0.97; odds ratio 0.75), and childhood obesity. Analysis of 645 trios with childhood obesity supported further the A76A T/C association, showing an overtransmission to obese children of the at risk T allele (59.0%; P = 0.01), especially in children with most severe forms of obesity (Z score of body mass index > 4) (67.0%; P = 0.003). The A76A at risk T allele was also associated with overeating during meals (P = 0.02) in an additional group of 102 nonobese children. None of the MCHR2 variants, including the A76A SNP, showed association with adult severe obesity, although a trend for association of the T allele of this variant with food disinhibition (P = 0.06) and higher hunger (P = 0.09) was found. This variant was not associated with childhood obesity in an independent case-control study, including 1,573 subjects (P = 0.98). Moreover, the A76A SNP did not explain the linkage on the 6q locus. CONCLUSION: Our results altogether suggest that MCHR2 is not a major contributor to polygenic obesity and support a modest effect of the A76A SNP on food intake abnormalities in childhood.

Published
2007
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5. Cellular localization of apelin and its receptor in the anterior pituitary: evidence for a direct stimulatory action of apelin on ACTH release

Author

Marie-Thérèse Bluet-Pajot, Rodrigo Alvear-Perez, Philippe Zizzari, Catherine Llorens-Cortes, Annabelle Réaux-Le Goazigo, Jacques Epelbaum, 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), Neurobiologie de la Croissance et de la Senescence, 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 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), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Collège de France ( CdF ) -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 ), and Llorens Cortes, Catherine

Subjects
Male, Pituitary gland, Endocrinology, Diabetes and Metabolism, MESH: Amino Acid Sequence, MESH: Receptors, G-Protein-Coupled, MESH: Base Sequence, MESH : Tissue Distribution, Receptors, G-Protein-Coupled, Rats, Sprague-Dawley, 0302 clinical medicine, MESH: Cricetulus, MESH: Pituitary Gland, MESH: Ligands, MESH : CHO Cells, Tissue Distribution, MESH: Animals, MESH: Peptide Fragments, MESH : Ligands, 0303 health sciences, MESH : Amino Acid Sequence, MESH : Cyclic AMP, MESH: Pituitary Gland, Anterior, MESH : Cricetinae, MESH : Protein Binding, [ SDV.MHEP.EM ] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Apelin, MESH : Adrenocorticotropic Hormone, Intercellular Signaling Peptides and Proteins, MESH : Carrier Proteins, medicine.medical_specialty, endocrine system, MESH : Cell Membrane, MESH : Cricetulus, MESH: Carrier Proteins, Adrenocorticotropic hormone, 03 medical and health sciences, Adrenocorticotropic Hormone, Anterior pituitary, Pituitary Gland, Anterior, MESH: CHO Cells, Physiology (medical), MESH: Protein Binding, MESH: Tissue Distribution, MESH: Adrenocorticotropic Hormone, MESH: Humans, MESH: Molecular Sequence Data, MESH : Humans, Peptide Fragments, Endocrinology, Carrier Proteins, 030217 neurology & neurosurgery, MESH : Molecular Sequence Data, Physiology, MESH: Corticotrophs, MESH: Cricetinae, MESH : Models, Biological, MESH: Rats, Sprague-Dawley, Rats, Inbred WKY, MESH : Pituitary Gland, Receptor, Corticotrophs, Cellular localization, MESH: Cyclic AMP, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Apelin Receptors, MESH : Rats, MESH : Forskolin, medicine.anatomical_structure, MESH: Pituitary Hormones, Anterior, MESH: Calcium, MESH : Receptors, G-Protein-Coupled, MESH : Transfection, MESH: Forskolin, hormones, hormone substitutes, and hormone antagonists, MESH: Rats, Inbred WKY, Endocrine gland, MESH: Rats, MESH : Male, MESH : Rats, Inbred WKY, Biology, Models, Biological, MESH : Pituitary Hormones, Anterior, MESH : Pituitary Gland, Anterior, Pituitary Hormones, Anterior, Internal medicine, medicine, Animals, MESH : Calcium, 030304 developmental biology, Apelin receptor, MESH: Transfection, MESH : Peptide Fragments, MESH: Models, Biological, MESH : Corticotrophs, MESH : Rats, Sprague-Dawley, MESH: Male, Rats, MESH : Peptide Hormones, MESH: Peptide Hormones, MESH : Base Sequence, MESH : Animals, MESH: Cell Membrane
Abstract

Apelin is a bioactive peptide recently identified as the endogenous ligand of the human orphan G protein-coupled receptor APJ. The presence of apelin-immunoreactive nerve fibers, together with the detection of apelin receptor mRNA in the parvocellular part of the paraventricular nucleus and the stimulatory action of apelin on corticotropin-releasing hormone release, indicate that apelin modulates adrenocorticotropin (ACTH) release via an indirect action on the hypothalamus. However, a direct action of apelin in the anterior pituitary cannot be excluded. Here, we provided evidence for the existence of an apelinergic system within the adult male rat pituitary gland. Double immunofluorescence staining indicated that apelin is highly coexpressed in the anterior pituitary, mainly in corticotrophs (96.5 ± 0.3%) and to a much lower extent in somatotropes (3.2 ± 0.2%). Using in situ hybridization combined with immunohistochemistry, a high expression of apelin receptor mRNA was also found in corticotrophs, suggesting a local interaction between apelin and ACTH. In an ex vivo perifusion system of anterior pituitaries, apelin 17 (K17F, 10−6M) significantly increased basal ACTH release by 41%, whereas apelin 10 (R10F, 10−6M), an inactive apelin fragment, was ineffective. In addition, K17F but not R10F induced a dose-dependent increase in K+-evoked ACTH release, with maximal increase being observed for a 10−6M concentration. Taken together, these data outline the potential role of apelin as an autocrine/paracrine-acting peptide on ACTH release and provide morphological and neuroendocrine basis for further studies that explore the physiological role of apelin in the regulation of anterior pituitary functions.

Published
2007
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6. Platelet-activating factor and normal or leukaemic haematopoiesis

Author

Laurence Guglielmi, Yves Denizot, Franck Trimoreau, Magali Donnard, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), and Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
MESH: Signal Transduction, Cancer Research, B Cells, MESH : Receptors, Cell Surface, MESH: Hematopoiesis, Paf Receptor, MESH: Receptors, G-Protein-Coupled, Receptors, G-Protein-Coupled, chemistry.chemical_compound, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Receptor, MESH: Receptors, Cell Surface, B-Lymphocytes, Leukemia, Hematology, Leukaemic Diseases, Haematopoiesis, medicine.anatomical_structure, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH : Receptors, G-Protein-Coupled, lipids (amino acids, peptides, and proteins), Signal Transduction, Stromal cell, NLM, Receptors, Cell Surface, Blast Cells, Platelet Membrane Glycoproteins, Biology, MESH : B-Lymphocytes, Precursor cell, MESH: B-Lymphocytes, MESH: Leukemia, medicine, Humans, Progenitor cell, Platelet Activating Factor, B cell, MESH : Signal Transduction, MESH: Platelet Activating Factor, MESH: Humans, Platelet-activating factor, MESH : Humans, MESH : Leukemia, MESH: Platelet Membrane Glycoproteins, Hematopoiesis, MESH : Hematopoiesis, chemistry, MESH : Platelet Activating Factor, Immunology, Cancer research, Bone marrow, Platelet-activating Factor, MESH : Platelet Membrane Glycoproteins
Abstract

Platelet-activating factor (PAF), a phospholipid mediator with a wide range of actions on mature leukocytes, acts directly during early human haematopoiesis by affecting the growth of haematopoietic progenitors and indirectly, by modulating cytokine synthesis by bone marrow stromal cells. At this time, its role during leukaemic diseases remains speculative. The lack of membrane PAF receptor (PAF-R) on leukaemic blasts suggest that this receptor represents a marker of mature cells and its membrane induction a consequence of cell maturation. While the couple PAF/PAF-R has been largely studied using B cell lines, few results are available using B cells of patients with haematopoietic malignancies casting some doubts concerning the potential role (if any) of this molecule during leukaemic diseases.

Published
2003
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7. Presence of membrane platelet-activating factor receptors on B cells of chronic B cell leukaemia patients

Author

Dominique Bordessoule, Magali Donnard, Franck Trimoreau, Arnaud Jaccard, Yves Denizot, Laurence Guglielmi, Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations ( PMRIL ), Université de Limoges ( UNILIM ) -Génomique, Environnement, Immunité, Santé, Thérapeutique ( GEIST FR CNRS 3503 ) -Centre National de la Recherche Scientifique ( CNRS ), Physiologie Moléculaire de la Réponse Immune et des Lymphoproliférations (PMRIL), and Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Cancer Research, NLM, MESH : Male, MESH : Aged, MESH : Receptors, Cell Surface, Receptors, Cell Surface, MESH: Receptors, G-Protein-Coupled, Platelet Membrane Glycoproteins, Receptors, G-Protein-Coupled, MESH : B-Lymphocytes, chemistry.chemical_compound, MESH: B-Lymphocytes, medicine, Humans, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, MESH : Middle Aged, Receptor, MESH: Leukemia, Lymphocytic, Chronic, B-Cell, B cell, MESH: Receptors, Cell Surface, Aged, MESH: Aged, B-Lymphocytes, MESH: Humans, MESH: Middle Aged, Platelet-activating factor, Chemistry, MESH : Humans, MESH: Platelet Membrane Glycoproteins, Hematology, Middle Aged, MESH : Leukemia, Lymphocytic, Chronic, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Molecular biology, MESH: Male, Membrane, medicine.anatomical_structure, Oncology, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Receptors, G-Protein-Coupled, MESH: Female, MESH : Platelet Membrane Glycoproteins
Published
2003
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8. Trends in histamine research: new functions during immune responses and hematopoiesis

Author

Malvyne Rolli-Derkinderen, Michel Arock, Elke Schneider, Michel Dy, Universität Klangenfurt, Alpen-Adria-Universität Klagenfurt [Klagenfurt, Austria], Laboratoire d'Informatique et d'Intelligence Artificielle, Institut National des Sciences Appliquées - Strasbourg ( INSA Strasbourg ), Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Université Louis Pasteur - Strasbourg I, Institute for Process control and Robotics, Universität Karlsruhe (TH), Cytokines, hématopoïèse et réponse immune ( CHRI ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Physiopathologie et pharmacologie cellulaires et moléculaires, Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biologie et de Pharmacologie Appliquée ( LBPA ), École normale supérieure - Cachan ( ENS Cachan ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Louis Pasteur - Strasbourg I, Cytokines, hématopoïèse et réponse immune (CHRI), 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 de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Biologie et de Pharmacologie Appliquée (LBPA), and École normale supérieure - Cachan (ENS Cachan)-Centre National de la Recherche Scientifique (CNRS)

Subjects
MESH: Hematopoiesis, MESH: Receptors, G-Protein-Coupled, MESH: Basophils, Receptors, G-Protein-Coupled, chemistry.chemical_compound, Histamine receptor, 0302 clinical medicine, Immunology and Allergy, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Mast Cells, Receptor, 0303 health sciences, MESH: Mast Cells, MESH : Research, Mast cell, 3. Good health, Basophils, MESH : Histamine, Haematopoiesis, medicine.anatomical_structure, MESH: Research, 030220 oncology & carcinogenesis, [SDV.IMM]Life Sciences [q-bio]/Immunology, Receptors, Histamine, MESH : Receptors, G-Protein-Coupled, MESH : Basophils, MESH : Mast Cells, MESH: Histamine, Histamine, Immunology, Histamine H1 receptor, Biology, Basophil degranulation, MESH : Receptors, Histamine, 03 medical and health sciences, Immune system, medicine, Animals, Humans, 030304 developmental biology, Receptors, Histamine H4, MESH: Humans, Research, MESH : Humans, Hematopoiesis, MESH : Hematopoiesis, MESH: Receptors, Histamine, chemistry, MESH : Animals
Abstract

Histamine is a bioamine with multiple physiological activities. In the immune system, it not only mediates the deleterious effects accompanying allergic reactions, but it acts also in a more subtle way by modulating the T helper 1 (Th1)–Th2 balance and possibly hematopoiesis. The histamine required for Th-cell polarization is provided by mast cell or basophil degranulation, as well as being newly synthesized and immediately released by other hematopoietic cells, in response to molecules generated during the immune response. Its global effect depends on the subtype and distribution of histamine receptors on target cells. The recent discovery of a novel H 4 receptor, which is expressed preferentially on immunocompetent cells, will have important consequences for the understanding of the regulatory functions of histamine during the immune response.

Published
2002

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