Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis
Bcl-2 prevents loss of mitochondria in CCCP-induced apoptosis
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DOI：
10.1016/j.yexcr.2004.06.024
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发表时间：
2004-10-01
影响因子：
3.7
通讯作者：
Jansen, JH
中科院分区：
文献类型：
--
作者：
de Graaf, AO;van den Heuvel, LP;Jansen, JH
Bcl-2家族蛋白在线粒体水平调节细胞凋亡。为了研究Bcl-2功能的机制，我们研究了质子载体羰基氰间氯苯腙（CCCP）对两种造血细胞系和Bcl-2过表达转染子的影响。CCCP直接干扰线粒体功能并诱导细胞凋亡。我们发现，Bcl-2抑制细胞凋亡和Bcl-2的抗凋亡作用发生上游的半胱天冬酶的激活和细胞凋亡相关的核变化，因为这些细胞过度表达Bcl-2显着抑制。Bcl-2不能阻止CCCP诱导的FL5.12和Jurkat细胞线粒体膜电位的降低和细胞ATP含量的改变。电子显微镜显示，与亲本细胞相比，在未处理的Bcl-2转染细胞中观察到更高数量的线粒体。暴露于CCCP导致线粒体数量急剧减少，线粒体超微结构严重破坏，亲代细胞明显肿胀和嵴丢失。Bcl-2明显减少了线粒体结构的破坏，并保留了更多的线粒体。这些数据表明，CCCP诱导细胞凋亡的线粒体结构破坏和Bcl-2防止细胞凋亡和线粒体变性，通过保护线粒体的完整性。(C)2004年爱思唯尔公司All rights reserved.
Bcl-2 family proteins regulate apoptosis at the level of mitochondria. To examine the mechanism of Bcl-2 function, we investigated the effects of the protonophore carbonyl cyanide m-chlorophenyl hydrazone (CCCP) on two hematopoietic cell lines and Bcl-2 overexpressing transfectants. CCCP directly interferes with mitochondrial function and induces apoptosis. We show that Bcl-2 inhibits apoptosis and that the antiapoptotic effect of Bcl-2 takes place upstream of caspase activation and nuclear changes associated with apoptosis, since these were markedly inhibited in cells overexpressing Bcl-2. Bcl-2 does not prevent the decrease in mitochondrial membrane potential nor the alterations in cellular ATP content induced by CCCP in FL5.12 and Jurkat cells. A higher number of mitochondria was observed in untreated Bcl-2 transfected cells compared to parental cells, as shown by electron microscopy. Exposure to CCCP induced a dramatic decrease in the number of mitochondria and severely disrupted mitochondrial ultrastructure, with apparent swelling and loss of cristae in parental cells. Bcl-2 clearly diminished the disruption of mitochondrial structure and preserved a higher number of mitochondria. These data suggest that CCCP induces apoptosis by structural disruption of mitochondria and that Bcl-2 prevents apoptosis and mitochondrial degeneration by preserving mitochondrial integrity. (C) 2004 Elsevier Inc. All rights reserved.