BCL-2 FUNCTIONS IN AN ANTIOXIDANT PATHWAY TO PREVENT APOPTOSIS
BCL-2 FUNCTIONS IN AN ANTIOXIDANT PATHWAY TO PREVENT APOPTOSIS
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DOI：
10.1016/0092-8674(93)80066-n
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发表时间：
1993-10-22
期刊：
影响因子：
64.5
通讯作者：
KORSMEYER, SJ
中科院分区：
文献类型：
--
作者：
HOCKENBERY, DM;OLTVAI, ZN;KORSMEYER, SJ
Bcl-2抑制大多数类型的凋亡性细胞死亡，这意味着一种常见的致死机制。Bcl-2定位于氧自由基产生的细胞内位点，包括线粒体、内质网和核膜。抗氧化剂，使过氧化物，N-乙酰半胱氨酸和谷胱甘肽过氧化物酶，对抗凋亡性死亡，而锰超氧化物歧化酶没有。Bcl-2保护细胞免受H2 O2和甲萘醌诱导的氧化死亡。Bcl-2不能阻止甲萘醌产生的抗氰化物氧化爆发。两个模型系统的细胞凋亡没有增加抗氰化物呼吸，和产生的内源性过氧化物继续在一个固有的速度是不变的Bcl-2。凋亡信号后，细胞持续进行性脂质过氧化。Bcl-2过表达可完全抑制脂质过氧化反应。我们提出了一个模型，其中Bcl-2调节抗氧化剂途径的网站的自由基生成。
Bcl-2 inhibits most types of apoptotic cell death, implying a common mechanism of lethality. Bcl-2 is localized to intracellular sites of oxygen free radical generation including mitochondria, endoplasmic reticula, and nuclear membranes. Antioxidants that scavenge peroxides, N-acetylcysteine and glutathione peroxidase, countered apoptotic death, while manganese superoxide dismutase did not. Bcl-2 protected cells from H2O2- and menadione-induced oxidative deaths. Bcl-2 did not prevent the cyanide-resistant oxidative burst generated by menadione. Two model systems of apoptosis showed no increment in cyanide-resistant respiration, and generation of endogenous peroxides continued at an inherent rate that was unaltered by Bcl-2. Following an apoptotic signal, cells sustained progressive lipid peroxidation. Overexpression of Bcl-2 functioned suppress lipid peroxidation completely. We propose a model in which Bcl-2 regulates an antioxidant pathway at sites of free radical generation.