Hyperosmotic shock induces cytochrome c release and caspase-3 activation in Xenopus oocytes. Different signaling pathways engaged by osmostress converge on the mitochondria to trigger cell death. The mitogen activated protein kinases (MAPKs) JNK1-1 and JNK1-2 are early activated by hyperosmotic shock and sustained activation of both isoforms accelerates the apoptotic program. Indeed, sustained activation of p38 accelerates osmostress-induced cell death, but the p38 isoforms involved are not well characterized. Here we study the expression and activation of Xenopus p38 isoforms in response to hyperosmotic stress. We find that p38α, p38β, and p38γ are early activated by hyperosmotic shock and sustained activation of p38α and p38β accelerates osmostress-induced apoptosis. Moreover, microinjection of cytochrome c in the oocytes induces caspase-3 activation and p38α and p38β phosphorylation suggesting that caspases and kinases are interlinked in a positive feedback loop to promote cell death. In summary, we present a more complete view of the mechanisms involved in osmostress-induced apoptosis.

中文翻译：

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p38α 和 p38β 调节 Osmostress 诱导的细胞凋亡。


高渗性休克诱导非洲爪蟾卵母细胞中细胞色素 c 的释放和 caspase-3 激活。渗透应激参与的不同信号通路汇聚在线粒体上以触发细胞死亡。丝裂原活化蛋白激酶 （MAPK） JNK1-1 和 JNK1-2 在高渗性休克的早期激活，两种亚型的持续激活会加速凋亡程序。事实上，p38 的持续激活会加速渗透压诱导的细胞死亡，但所涉及的 p38 亚型尚未得到很好的表征。在这里，我们研究了非洲爪蟾 p38 亚型响应高渗应激的表达和激活。我们发现 p38α 、 p38β 和 p38γ 早期被高渗休克激活，p38α 和 p38β 的持续激活加速渗透压诱导的细胞凋亡。此外，在卵母细胞中显微注射细胞色素 c 可诱导 caspase-3 激活以及 p38α 和 p38β 磷酸化，表明 caspase 和激酶在正反馈回路中相互连接以促进细胞死亡。总之，我们更完整地介绍了渗透压诱导的细胞凋亡所涉及的机制。