Osmostress-induced apoptosis in Xenopus oocytes: role of stress protein kinases, calpains and Smac/DIABLO.
Osmostress-induced apoptosis in Xenopus oocytes: role of stress protein kinases, calpains and Smac/DIABLO.
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渗透压诱导的异武卵母细胞的凋亡：应激蛋白激酶，calpains和Smac/Diablo的作用。
DOI：
10.1371/journal.pone.0124482
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
López JM
中科院分区：
文献类型：
--
作者：
Ben Messaoud N;Yue J;Valent D;Katzarova I;López JM
高渗休克可诱导非洲爪哇卵母细胞释放细胞色素c和激活Capase-3，但涉及的调控因子和信号转导途径尚不清楚。在此，我们发现高渗休克可诱导钙激活蛋白迅速激活，并在大量细胞色素c被释放以促进caspase-3激活之前从线粒体释放高水平的Smac/DIABLO。钙蛋白酶抑制剂或EGTA微量注射延缓渗透应激诱导的细胞凋亡，而抗体阻断Smac/Diablo显著减少细胞色素c的释放和caspase-3的激活。高渗休克还可以非常迅速地激活p38和JNK信号通路。同时抑制p38和JNK通路可减少渗透应激诱导的细胞凋亡，而持续激活这些通路则加速细胞色素c的释放和caspase-3的激活。因此，渗透应激早期诱导的至少四种不同途径汇聚在线粒体上，触发细胞凋亡。破译高渗休克诱导细胞凋亡的机制为人类疾病的潜在治疗提供了洞察力，这些疾病是由液体渗透压扰动引起的。
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.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
Bennett, BL;Sasaki, DT;Anderson, DW
通讯作者：
Anderson, DW
影响因子：
11.4
作者：
Adrain, C;Creagh, EM;Martin, SJ
通讯作者：
Martin, SJ
影响因子：
64.5
作者：
Du, CY;Fang, M;Wang, XD
通讯作者：
Wang, XD
影响因子：
56.9
作者：
MINDEN, A;LIN, A;KARIN, M
通讯作者：
KARIN, M
影响因子：
11.4
作者：
Kluck, RM;Martin, SJ;Newmeyer, DD
通讯作者：
Newmeyer, DD