MT-21 is a synthetic apoptosis inducer that directly induces cytochrome c release from mitochondria.
MT-21 is a synthetic apoptosis inducer that directly induces cytochrome c release from mitochondria.
复制标题
MT-21 是一种合成的细胞凋亡诱导剂，可直接诱导线粒体释放细胞色素 c。
作者：
M. Watabe;K. Machida;H. Osada
我们以前报道过，一种合成化合物MT-21通过激活Krs/MST蛋白的c-Jun-NH 2-末端激酶诱导细胞凋亡，该蛋白由依赖于活性氧产生的caspase-3裂解激活。在这里，我们研究的激活机制，半胱氨酸天冬氨酸蛋白酶-3，一个重要的半胱氨酸天冬氨酸蛋白酶，在MT-21诱导的细胞凋亡。我们发现MT-21通过caspase-9激活caspase-3，但不通过caspase-8。此外，MT-21诱导细胞色素c从线粒体中释放，这是激活caspase-9所必需的，并且这种释放发生在膜电位变化之前。MT-21诱导的细胞凋亡的起始过程被Bcl-2的过表达抑制，Bcl-2已知阻止细胞响应于各种刺激而经历细胞凋亡。此外，当我们用MT-21处理从细胞中分离的线粒体时，观察到细胞色素c从线粒体中直接释放，而在从过表达Bcl-2的细胞中分离的线粒体中没有观察到这种效果。已知通过从线粒体释放细胞色素c诱导细胞凋亡的其他细胞凋亡诱导剂不能直接从分离的线粒体释放细胞色素c。这些发现表明MT-21是一种可能的候选抗肿瘤剂，其能够通过从线粒体直接释放细胞色素c来诱导细胞凋亡。
We reported previously that a synthetic compound, MT-21, induced apoptosis by activating c-Jun-NH2-terminal kinase via the Krs/MST protein, which is activated by caspase-3 cleavage dependent on reactive oxygen species production. Here we examine the activation mechanism of caspase-3, an important cysteine aspartic protease, during MT-21-induced apoptosis. We found that MT-21 activated caspase-3 via caspase-9, but not via caspase-8. In addition, MT-21 induced the release of cytochrome c from the mitochondria that is necessary to activate caspase-9, and this release occurred before a change in membrane potential. This initiation process of MT-21-induced apoptosis was suppressed by overexpression of Bcl-2, which is known to prevent cells from undergoing apoptosis in response to a variety of stimuli. Moreover, when we treated mitochondria isolated from the cells with MT-21, the direct release of cytochrome c from the mitochondria was observed, whereas this effect was not observed in the mitochondria isolated from cells that overexpressed Bcl-2. Other apoptosis-inducing agents known to induce apoptosis via cytochrome c release from the mitochondria failed to release cytochrome c directly from isolated mitochondria. These findings indicate that MT-21 is a possible candidate antitumor agent that is able to induce apoptosis via the direct release of cytochrome c from the mitochondria.
影响因子：
10.5
作者：
Wang, K;Yin, XM;Korsmeyer, SJ
通讯作者：
Korsmeyer, SJ
影响因子：
16
作者：
Yang, XL;Chang, HY;Baltimore, D
通讯作者：
Baltimore, D
DOI：
10.1073/pnas.93.19.10099
发表时间：
1996-09-17
影响因子：
11.1
作者：
Taylor, LK;Wang, HCR;Erikson, RL
通讯作者：
Erikson, RL