title: P35-sensitive caspases, MAP kinases and Rho modulate beta-adrenergic induction of apoptosis in mollusc immune cells.
abstract: Apoptosis is an important mechanism for the preservation of a healthy and balanced immune system in vertebrates. Little is known, however, about how apoptotic processes regulate invertebrate immune defenses. In the present study, we show that noradrenaline, a catecholamine produced by the neuroendocrine system and by immune cells in molluscs, is able to induce apoptosis of oyster Crassostrea gigas hemocytes. The apoptosis-inducing effect of noradrenaline was mimicked by isoproterenol and blocked by propranolol, which indicates that noradrenaline triggers apoptosis via a beta-adrenergic signaling pathway. Exposure to the pan-caspase inhibitor Z-VAD-FMK or expression of the caspase inhibitor P35 under the transcriptional control of a mollusc hsp70 gene promoter reduced the number of apoptotic cells among noradrenaline-treated hemocytes. These results suggest that P35-sensitive caspases are involved in the apoptotic process triggered by beta-adrenergic signaling. Complementary experiments suggest that mitogen-activated protein kinases and Rho, a member of the Ras GTPase family, may be involved in antiapoptotic mechanisms that modulate the apoptotic effect of noradrenaline. Taken together, these results provide a first insight into apoptotic processes in mollusc immune cells.
authors.affiliation: Station Biologique de Roscoff, CNRS, Université Paris VI, INSU Place Georges Teissier, B.P. 74, F-29682 Roscoff cedex, France. lacoste@itsa.ucsf.edu
authors.forename: Arnaud
authors.initials: A
authors.lastname: Lacoste
authors.forename: Anne
authors.initials: A
authors.lastname: Cueff
authors.forename: Serge A
authors.initials: SA
authors.lastname: Poulet
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006434:Hemocytes / Q000187:drug effects / Q000276:immunology* / Q000648:ultrastructure; D051034:Inhibitor of Apoptosis Proteins; D020935:MAP Kinase Signaling System; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008974:Mollusca / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D009638:Norepinephrine / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D015398:Signal Transduction; D014764:Viral Proteins / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
chemical_list: D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D051034:Inhibitor of Apoptosis Proteins; D014764:Viral Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C086430:inhibitor of apoptosis, Nucleopolyhedrovirus; D011433:Propranolol; D020928:Mitogen-Activated Protein Kinases; D020741:rho GTP-Binding Proteins; D009638:Norepinephrine