Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced apoptosis.
Bax deficiency affects caspase-2 activation during ultraviolet radiation-induced apoptosis.
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Bax 缺陷会影响紫外线辐射诱导的细胞凋亡过程中 caspase-2 的激活。
DOI：
10.1038/sj.onc.1207212
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发表时间：
2004
期刊：
影响因子：
--
通讯作者：
Sheikh,MSaeed
中科院分区：
文献类型：
--
作者：
He,Qin;Huang,Ying;Sheikh,MSaeed
关于 caspase-2 是启动子还是效应子 caspase，一直存在相当大的争论。最近，提出了一种新的细胞凋亡内在途径模型，表明 caspase-2 是 caspase 的启动子。例如，紫外线 (UV) 和其他 DNA 损伤诱导剂被证明首先激活 caspase-2，然后调节线粒体和线粒体后事件。研究发现活性 caspase-2 通过促进 Bax 易位至线粒体来与线粒体结合。因此，Bax 被认为通过影响线粒体通透性、细胞色素 c 释放到细胞质中以及 caspase-9 激活，在桥接活性 caspase-2 与线粒体方面发挥核心作用。在本研究中，我们研究了 Bax 在紫外线诱导的细胞凋亡和 caspase-2 激活中的作用。我们的结果表明，在 Bax 缺陷细胞中，紫外线诱导的细胞凋亡和 caspase-2 激活减弱，这表明 Bax 似乎在紫外线诱导的细胞凋亡以及 caspase-2 激活中发挥重要作用，并且它似乎也位于 caspase-2 的上游。 Bax 缺陷还影响了 caspase-3 和-8 的激活，并在 UV 诱导的细胞凋亡过程中消除了 caspase-9 的激活，这表明 caspase-9 激活的缺失可能会影响 Bax 缺陷细胞中 caspase-2、-3 和 -8 的激活。根据我们的结果，我们提出半胱天冬酶的激活不是线性级联事件，而是通过复杂的反馈回路连接。
There has been a considerable debate as to whether caspase-2 is an initiator or effector caspase. Recently, a new model of intrinsic pathway of apoptosis has been proposed, which suggests caspase-2 to be an initiator caspase. For example, ultraviolet radiation (UV) and other DNA damage-inducing agents were shown to first activate caspase-2 and then regulate the mitochondrial and postmitochondrial events. Active caspase-2 was found to engage mitochondria by promoting Bax translocation to the mitochondria. Consequently, Bax was proposed to play a central role in bridging the active caspase-2 with mitochondria by affecting mitochondrial permeability, cytochrome c release into the cytosol and caspase-9 activation. In the present study, we investigated the role of Bax in UV-induced apoptosis and caspase-2 activation. Our results indicate that UV-induced apoptosis and caspase-2 activation were diminished in Bax-deficient cells, suggesting that Bax appears to play an important role in UV-induced apoptosis as well as caspase-2 activation, and that it also appears to reside upstream of caspase-2. Bax deficiency also affected the activation of caspase-3 and-8 and abolished caspase-9 activation during UV-induced apoptosis, suggesting that the absence of caspase-9 activation may affect caspase-2,-3 and-8 activation in Bax-deficient cells. Based on our results, we propose that activation of caspases is not a linear cascade of events, but is rather connected via complex feedback loops.