Caspases 3 and 7: Key mediators of mitochondrial events of apoptosis
Caspases 3 and 7: Key mediators of mitochondrial events of apoptosis
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DOI：
10.1126/science.1115035
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发表时间：
2006-02-10
期刊：
影响因子：
56.9
通讯作者：
Flavell, RA
中科院分区：
文献类型：
--
作者：
Lakhani, SA;Masud, A;Flavell, RA
目前的细胞凋亡模型认为，上游信号导致下游效应半胱氨酸天冬氨酸酶的激活。我们培育了两种效应器caspase 3和caspase 7缺陷的小鼠，这些小鼠出生后立即死于心脏发育缺陷。缺乏这两种酶的成纤维细胞对线粒体和死亡受体介导的细胞凋亡都具有高度的抵抗力，表现出线粒体膜电位的保存，并存在凋亡诱导因子(AIF)的核转位缺陷。此外，Bax易位和细胞色素c释放的早期凋亡事件也被推迟。我们得出结论，caspase3和caspase7是线粒体凋亡事件的关键介质。
The current model of apoptosis holds that upstream signals lead to activation of downstream effector caspases. We generated mice deficient in the two effectors, caspase 3 and caspase 7, which died immediately after birth with defects in cardiac development. Fibroblasts lacking both enzymes were highly resistant to both mitochondrial and death receptor-mediated apoptosis, displayed preservation of mitochondrial membrane potential, and had defective nuclear translocation of apoptosis-inducing factor (AIF). Furthermore, the early apoptotic events of Bax translocation and cytochrome c release were also delayed. We conclude that caspases 3 and 7 are critical mediators of mitochondrial events of apoptosis.