Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia
Release of caspase-9 from mitochondria during neuronal apoptosis and cerebral ischemia
复制标题
DOI：
10.1073/pnas.96.10.5752
复制
发表时间：
1999-05-11
影响因子：
11.1
通讯作者：
Reed, JC
中科院分区：
文献类型：
--
作者：
Krajewski, S;Krajewska, M;Reed, JC
Caspase-9对细胞色素c（cyto-c）依赖性凋亡和正常脑发育至关重要。我们确定，这种顶端蛋白酶在细胞凋亡的cyto-c途径驻留在线粒体内的几种类型的细胞，包括心肌细胞和许多神经元。Caspase-9在用Ca 2+或Bar处理时从分离的线粒体释放，所述Ca 2+或Bar是已知诱导线粒体释放cyto-c的缺血性神经元细胞死亡中涉及的刺激。在神经元细胞培养模型中，凋亡诱导剂触发caspase-9从线粒体易位到细胞核，这可被Bcl-2所诱导。类似地，在短暂性全脑缺血的动物模型中，在海马和其他表现出凋亡前的早期缺血后变化的脆弱神经元中观察到caspase-9从线粒体释放并在细胞核中积累。因此，在缺血或其他损伤引起的神经元损伤过程中，线粒体屏障功能的丧失可能在使某些半胱天冬酶参与细胞凋亡中发挥重要作用。
Caspase-9 is critical for cytochrome c (cyto-c)-dependent apoptosis and normal brain development. We determined that this apical protease in the cyto-c pathway for apoptosis resides inside mitochondria in several types of cells, including cardiomyocytes and many neurons. Caspase-9 is released from isolated mitochondria on treatment with Ca2+ or Bar, stimuli implicated in ischemic neuronal cell death that are known to induce cyto-c release from mitochondria. In neuronal cell culture models, apoptosis-inducing agents trigger translocation of caspase-9 from mitochondria to the nucleus, which is inhibitable by Bcl-2, Similarly, in an animal model of transient global cerebral ischemia, caspase-9 release from mitochondria and accumulation in nuclei was observed in hippocampal and other vulnerable neurons exhibiting early postischemic changes preceding apoptosis. Loss of mitochondrial barrier function during neuronal damage from ischemia or other insults therefore may play an important role in making certain caspases available to participate in apoptosis.