Early activation of the mitochondrial apoptotic pathway in Vesicular Stomatitis Virus-infected cells
Early activation of the mitochondrial apoptotic pathway in Vesicular Stomatitis Virus-infected cells
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DOI：
10.1016/j.virusres.2004.10.007
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发表时间：
2005-04-01
期刊：
影响因子：
5
通讯作者：
Coulombié, F
中科院分区：
文献类型：
--
作者：
Gadaleta, P;Perfetti, X;Coulombié, F
水泡性口炎病毒（VSV）已被证明可以以半胱天冬酶依赖的方式诱导细胞凋亡，但确切的凋亡途径仍然未知。我们发现，半胱天冬酶9和3，但不是半胱天冬酶8，被激活的VSV诱导的细胞凋亡在感染的Vero细胞。由于caspase 9与线粒体凋亡途径相关，我们分析了一些线粒体事件，如线粒体跨膜电位（Deltapsi（m））的变化和线粒体释放的促凋亡蛋白，如细胞色素c和凋亡诱导因子（AIF）。我们发现，VSV感染触发Deltapsi（m）的消散和细胞色素c和AIF从线粒体膜间隙的释放非常早在VSV感染。这些结果表明，触发VSV感染的细胞凋亡发生通过线粒体凋亡途径的早期激活。另一方面，在病毒感染期间评估抗凋亡蛋白如Bcl-2和Bcl-xL以及促凋亡蛋白Bax的细胞内水平。这些分析表明，随着病毒感染的进行，Bcl-xL的细胞水平下降，而Bax和Bcl-2的水平保持不受影响。本文还讨论了Bcl-xL调制的意义。(C)2004 Elsevier B. V.保留所有权利。
Vesicular Stomatitis Virus (VSV) has been shown to induce apoptosis in a caspase-dependent manner, but the precise apoptotic pathway remains unknown. We found that caspases 9 and 3, but not caspase 8, were activated during VSV-induced apoptosis in infected Vero cells. Since caspase 9 is related to the mitochondrial apoptotic pathway, we analyzed some mitochondrial events such as changes in the mitochondrial transmembrane potential (Deltapsi(m)) and mitochondrial release of apoptogenic proteins such as cytochrome c and the apoptosis inducing factor (AIF). We found that VSV infection triggers the dissipation of the Deltapsi(m) and the release of both cytochrome c and AIF from the mitochondrial intermembrane space very early in the VSV infection. These results indicate that the trigger of apoptosis in VSV-infected cells occurs through the early activation of the mitochondrial apoptotic pathway. On the other hand, intracellular levels of the anti-apoptotic proteins, such as Bcl-2 and Bcl-xL, and the pro-apoptotic protein Bax, were assessed during viral infection. These analyses showed that as viral infection proceeded, the cellular level of Bcl-xL decreased, while the levels of Bax and Bcl-2 remained unaffected. The significance of the Bcl-xL modulation is also discussed. (C) 2004 Elsevier B.V. All rights reserved.