Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.
Inhibition of apoptosis in chlamydia-infected cells: blockade of mitochondrial cytochrome c release and caspase activation.
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DOI：
10.1084/jem.187.4.487
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发表时间：
1998-02-16
期刊：
影响因子：
--
通讯作者：
Zhong G
中科院分区：
文献类型：
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作者：
Fan T;Lu H;Hu H;Shi L;McClarty GA;Nance DM;Greenberg AH;Zhong G
我们报道，衣原体是一种专性的细胞内细菌病原体，具有一种新的抗凋亡机制。衣原体感染的宿主细胞对广泛的促凋亡刺激具有深刻的抵抗力，包括激酶抑制剂星形孢子素、DNA损伤剂依托泊苷，以及几种免疫凋亡诱导分子，如肿瘤坏死因子-α、Fas抗体和颗粒酶B/穿孔素。抗细胞凋亡活性依赖于衣原体的合成，而不依赖于宿主蛋白的合成。这些观察表明，衣原体可能编码的因子可以中断许多不同的宿主细胞凋亡途径。我们发现在衣原体感染的细胞中，caspase3下游的激活和聚(ADP-核糖)聚合酶的切割都受到抑制。衣原体感染也能阻止促凋亡因子诱导的线粒体细胞色素c释放到胞浆中。这些观察表明，衣原体蛋白可能通过阻止线粒体细胞色素c的释放来阻断不同的凋亡途径，这是一个中心步骤，被认为是将上游专用途径转化为下游caspase扩增的效应凋亡途径。因此，我们已经确定了衣原体的抗凋亡机制(S)，这将有助于确定衣原体的发病机制，并可能提供关于调节宿主细胞凋亡的中枢机制的信息。
We report that chlamydiae, which are obligate intracellular bacterial pathogens, possess a novel antiapoptotic mechanism. Chlamydia-infected host cells are profoundly resistant to apoptosis induced by a wide spectrum of proapoptotic stimuli including the kinase inhibitor staurosporine, the DNA-damaging agent etoposide, and several immunological apoptosis-inducing molecules such as tumor necrosis factor-α, Fas antibody, and granzyme B/perforin. The antiapoptotic activity was dependent on chlamydial but not host protein synthesis. These observations suggest that chlamydia may encode factors that interrupt many different host cell apoptotic pathways. We found that activation of the downstream caspase 3 and cleavage of poly (ADP-ribose) polymerase were inhibited in chlamydia-infected cells. Mitochondrial cytochrome c release into the cytosol induced by proapoptotic factors was also prevented by chlamydial infection. These observations suggest that chlamydial proteins may interrupt diverse apoptotic pathways by blocking mitochondrial cytochrome c release, a central step proposed to convert the upstream private pathways into an effector apoptotic pathway for amplification of downstream caspases. Thus, we have identified a chlamydial antiapoptosis mechanism(s) that will help define chlamydial pathogenesis and may also provide information about the central mechanisms regulating host cell apoptosis.