Mechanism of nitric oxide-induced apoptosis in human neuroblastoma SH-SY5Y cells
Mechanism of nitric oxide-induced apoptosis in human neuroblastoma SH-SY5Y cells
复制标题
DOI：
10.1016/s0014-5793(00)02167-0
复制
发表时间：
2000-11-10
期刊：
影响因子：
3.5
通讯作者：
Nomura, Y
中科院分区：
文献类型：
--
作者：
Moriya, R;Uehara, T;Nomura, Y
我们试图阐明一氧化氮（NO）诱导神经元细胞凋亡的精确机制。通过 NO 处理观察到 DEVD-AFC、VDVAD-AFC 和 LEHD-AFC（分别是 caspase-3 样蛋白酶（caspase-3 和 -7）、caspase-2 和 caspase-9 的特定底物）的酶裂解。 Western blot 分析显示，凋亡过程中 caspase-2、-3、-6 和 -7 的前体形式减少。有趣的是，Ac-DEVD-CHO，一种类似 caspase-3 的蛋白酶抑制剂，不仅可以阻断 caspase-2 和 -7 的减少，还可以阻断 NO 诱导的 caspase-3 中 p20 形成 p17，这表明 caspase-3 存在于 caspase-2 和 -7 的上游。没有。因此，NO 通过线粒体膜电位的连续损失、半胱天冬酶激活和半胱天冬酶激活的 DNase (CAD) 抑制剂的降解而导致神经元凋亡，(C) 2000 年欧洲生化协会联合会。由 Elsevier Science B.V 出版，保留所有权利。
We have attempted to elucidate the precise mechanism of nitric oxide (NO)-induced apoptotic neuronal cell death. Enzymatic cleavages of DEVD-AFC, VDVAD-AFC, and LEHD-AFC (specific substrates for caspase-3-like protease (caspase-3 and -7), caspase-2, and caspase-9, respectively) were observed by treatment with NO. Western blot analysis showed that pro-forms of caspase-2, -3, -6, and -7 are decreased during apoptosis. Interestingly, Ac-DEVD-CHO, a caspase-3-like protease inhibitor, blocked not only the decreases in caspase-2 and -7, but also the formation of p17 from p20 in caspase-3 induced by NO, suggesting that caspase-3 exists upstream of caspase-2 and -7, Bongkrekic acid, a potent inhibitor of mitochondrial permeability transition, specifically blocked both the loss of mitochondrial membrane potential and subsequent DNA fragmentation in response to NO. Thus, NO results in neuronal apoptosis through the sequential loss of mitochondrial membrane potential, caspase activation, and degradation of inhibitor of caspase-activated DNase (CAD) (CAD activation), (C) 2000 Federation of European Biochemical Societies. Published by Elsevier Science B.V, All rights reserved.