Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release.
Postnatal brain development and neural cell differentiation modulate mitochondrial Bax and BH3 peptide-induced cytochrome c release.
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出生后大脑发育和神经细胞分化调节线粒体 Bax 和 BH3 肽诱导的细胞色素 c 释放。
DOI：
10.1038/sj.cdd.4401158
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Fiskum,G
中科院分区：
文献类型：
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作者：
Polster,BM;Robertson,CL;Bucci,CJ;Suzuki,M;Fiskum,G
Bax介导神经发育过程中细胞色素c的释放和细胞凋亡。从8天，17天，和成年大鼠分离的脑线粒体显示线粒体Bax的水平下降。由含有BH 3细胞死亡结构域的肽从脑线粒体释放的细胞色素c的量随着年龄的增加而减少。然而，约60%的细胞色素c在成人脑线粒体中可以释放的BH 3肽在外源性人重组Bax的存在下。线粒体Bax下调与神经生长因子分化的PC 12 S神经细胞，从这些细胞中分离的线粒体表现出降低的敏感性BH 3-肽诱导的细胞色素c的释放。这些结果表明，未成熟的脑线粒体和未分化的神经细胞的线粒体是特别敏感的内源性Bax和BH 3死亡结构域肽介导的细胞色素c的释放。出生后线粒体Bax水平的发育变化可能有助于增加易感性的神经元病理性凋亡在未成熟的动物。
Bax mediates cytochrome c release and apoptosis during neurodevelopment. Brain mitochondria that were isolated from 8-day, 17-day, and adult rats displayed decreasing levels of mitochondrial Bax. The amount of cytochrome c released from brain mitochondria by a peptide containing the BH3 cell death domain decreased with increasing age. However, approximately 60% of cytochrome c in adult brain mitochondria could be released by the BH3 peptide in the presence of exogenous human recombinant Bax. Mitochondrial Bax was downregulated in PC12S neural cells differentiated with nerve growth factor, and mitochondria isolated from these cells demonstrated decreased sensitivity to BH3-peptide-induced cytochrome c release. These results demonstrate that immature brain mitochondria and mitochondria from undifferentiated neural cells are particularly sensitive to cytochrome c release mediated by endogenous Bax and a BH3 death domain peptide. Postnatal developmental changes in mitochondrial Bax levels may contribute to the increased susceptibility of neurons to pathological apoptosis in immature animals.