Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells
Caspase-8 and Apaf-1-independent caspase-9 activation in Sendai virus-infected cells
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DOI：
10.1074/jbc.m111898200
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发表时间：
2002-08-16
影响因子：
4.8
通讯作者：
Lauer, UM
中科院分区：
文献类型：
--
作者：
Bitzer, M;Armeanu, S;Lauer, UM
细胞凋亡性死亡在病毒感染的发病机制中起着核心作用。半胱氨酸蛋白酶的激活，即半胱氨酸酶，在病毒诱导的细胞凋亡效应阶段起关键作用。然而，对病毒感染的宿主细胞中导致启动子半胱氨酸酶激活的途径知之甚少。最近，我们发现仙台病毒(SeV)感染通过激活效应因子caspase-3和启动子caspase-8来触发细胞凋亡。我们现在研究了导致另一种启动子caspase-9激活的机制。出乎意料的是，我们发现caspase-9的切割并不依赖于活性caspase-3或-8的存在。此外，Caspase-9在小鼠胚胎成纤维细胞(MEF)中的存在是仙台病毒诱导细胞凋亡的先决条件。Caspase-9的激活不需要线粒体释放细胞色素c，也不依赖于APAF-1或活性氧中间体的存在。因此，我们的结果表明，在病毒感染的细胞中，除了通过死亡受体或线粒体细胞色素c释放的已知途径之外，还有另一种激活caspase-9的机制。
Apoptotic cell death is of central importance in the pathogenesis of viral infections. Activation of a cascade of cysteine proteases, i.e. caspases, plays a key role in the effector phase of virus-induced apoptosis. However, little is known about pathways leading to the activation of initiator caspases in virus-infected host cells. Recently, we have shown that Sendai virus (SeV) infection triggers apoptotic cell death by activation of the effector caspase-3 and initiator caspase-8. We now investigated mechanisms leading to the activation of another initiator caspase, caspase-9. Unexpectedly we found that caspase-9 cleavage is not dependent on the presence of active caspases-3 or -8. Furthermore, the presence of caspase-9 in mouse embryonic fibroblast (MEF) cells was a prerequisite for Sendai virus-induced apoptotic cell death. Caspase-9 activation occurred without the release of cytochrome c from mitochondria and was not dependent on the presence of Apaf-1 or reactive oxygen intermediates. Our results therefore suggest an alternative mechanism for caspase-9 activation in virally infected cells beside the well characterized pathways via death receptors or mitochondrial cytochrome c release.