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首页> 外文期刊>American Journal of Physiology >Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c.
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Polyamine depletion prevents camptothecin-induced apoptosis by inhibiting the release of cytochrome c.

机译：多胺耗竭通过抑制细胞色素c的释放来防止喜树碱诱导的细胞凋亡。

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We have shown previously that depletion of polyamines delays apoptosis induced by camptothecin in rat intestinal epithelial cells (IEC-6). Mitochondria play an important role in the regulation of apoptosis in mammalian cells because apoptotic signals induce mitochondria to release cytochrome c. The latter interacts with Apaf-1 to activate caspase-9, which in turn activates downstream caspase-3. Bcl-2 family proteins are involved in the regulation of cytochrome c release from mitochondria. In this study, we examined the effects of polyamine depletion on the activation of the caspase cascade, release of cytochrome c from mitochondria, and expression and translocation of Bcl-2 family proteins. We inhibited ornithine decarboxylase, the first rate-limiting enzyme in polyamine synthesis, with alpha-difluoromethylornithine (DFMO) to deplete cells of polyamines. Depletion of polyamines prevented camptothecin-induced release of cytochrome c from mitochondria and decreased the activity of caspase-9 and caspase-3. The mitochondrial membrane potential was not disrupted when cytochrome c was released. Depletion of polyamines decreased translocation of Bax to mitochondria during apoptosis. The expression of antiapoptotic proteins Bcl-x(L) and Bcl-2 was increased in DFMO-treated cells. Caspase-8 activity and cleavage of Bid were decreased in cells depleted of polyamines. These results suggest that polyamine depletion prevents IEC-6 cells from apoptosis by preventing the translocation of Bax to mitochondria, thus preventing the release of cytochrome c.
机译：以前我们已经表明，多胺的消耗延迟了喜树碱在大鼠肠上皮细胞（IEC-6）中诱导的凋亡。线粒体在哺乳动物细胞凋亡的调节中起重要作用，因为凋亡信号诱导线粒体释放细胞色素c。后者与Apaf-1相互作用以激活caspase-9，后者又激活下游caspase-3。 Bcl-2家族蛋白参与线粒体细胞色素C释放的调控。在这项研究中，我们检查了多胺耗竭对半胱天冬酶级联反应的激活，线粒体中细胞色素c的释放以及Bcl-2家族蛋白表达和转运的影响。我们抑制鸟氨酸脱羧酶，多胺合成中的第一个限速酶，用α-二氟甲基鸟氨酸（DFMO）来消耗多胺细胞。多胺的消耗阻止了喜树碱诱导的线粒体细胞色素c的释放，并降低了caspase-9和caspase-3的活性。释放细胞色素c时，线粒体膜电位不会被破坏。多胺的消耗减少了凋亡过程中Bax向线粒体的转运。在DFMO处理的细胞中，抗​​凋亡蛋白Bcl-x（L）和Bcl-2的表达增加。在缺乏多胺的细胞中，Caspase-8活性和Bid切割均降低。这些结果表明，多胺耗竭通过阻止Bax易位至线粒体，从而阻止了细胞色素c的释放，从而阻止了IEC-6细胞的凋亡。

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