title: Osmostress-induced apoptosis in Xenopus oocytes: role of stress protein kinases, calpains and Smac/DIABLO.
abstract: Hyperosmotic shock induces cytochrome c release and caspase-3 activation in Xenopus oocytes, but the regulators and signaling pathways involved are not well characterized. Here we show that hyperosmotic shock induces rapid calpain activation and high levels of Smac/DIABLO release from the mitochondria before significant amounts of cytochrome c are released to promote caspase-3 activation. Calpain inhibitors or EGTA microinjection delays osmostress-induced apoptosis, and blockage of Smac/DIABLO with antibodies markedly reduces cytochrome c release and caspase-3 activation. Hyperosmotic shock also activates the p38 and JNK signaling pathways very quickly. Simultaneous inhibition of both p38 and JNK pathways reduces osmostress-induced apoptosis, while sustained activation of these kinases accelerates the release of cytochrome c and caspase-3 activation. Therefore, at least four different pathways early induced by osmostress converge on the mitochondria to trigger apoptosis. Deciphering the mechanisms of hyperosmotic shock-induced apoptosis gives insight for potential treatments of human diseases that are caused by perturbations in fluid osmolarity.
authors: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors: Nabil
authors: N
authors: Ben Messaoud
authors: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors: Jicheng
authors: J
authors: Yue
authors: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors: Daniel
authors: D
authors: Valent
authors: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors: Ilina
authors: I
authors: Katzarova
authors: Institut de Neurociències, Departament de Bioquímica i Biologia Molecular, Unitat de Bioquímica, Facultad de Medicina, Universitat Autònoma de Barcelona, 08193 Cerdanyola del Vallès, Barcelona, Spain.
authors: José M
authors: JM
authors: López
mesh_terms: D000818:Animals; D017209:Apoptosis; D002154:Calpain / Q000378:metabolism*; D005260:Female; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009865:Oocytes / Q000166:cytology*; D009997:Osmotic Pressure; D015398:Signal Transduction; D029867:Xenopus Proteins / Q000378:metabolism*; D014982:Xenopus laevis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: C520098:DIABLO protein, Xenopus; D024101:Mitochondrial Proteins; D029867:Xenopus Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D002154:Calpain