Título:
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Osmostress-Induced Apoptosis in Xenopus Oocytes : Role of Stress Protein Kinases, Calpains and Smac/DIABLO
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Autor/a:
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Ben Messaoud, Nabil; Yue, Jicheng; Valent, Daniel; Katzarova, Ilina; López Blanco, José Manuel
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Abstract:
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Hyperosmotic shock induces cytochrome c release and capase-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. |
Materia(s):
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-Xenopus oocytes -Apoptosis -Mitochondria -Oocytes -Osmotic shock -Phosphorylation -Protein kinases -Cytosol |
Derechos:
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open access
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Tipo de documento:
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Article |
Editor:
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Uri:
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https://ddd.uab.cat/record/170666
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