期刊
FREE RADICAL BIOLOGY AND MEDICINE
卷 37, 期 11, 页码 1845-1853出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2004.09.005
关键词
free radicals; hydrogen peroxide; digitonin; apoptosis; necrosis; complex I; antioxidant
资金
- NIEHS NIH HHS [ES11838] Funding Source: Medline
- NINDS NIH HHS [NS34152] Funding Source: Medline
Bcl-2 family proteins protect against a variety of forms of cell death, including acute oxidative stress. Previous studies have shown that overexpression of the antiapoptotic protein Bcl-2 increases cellular redox capacity. Here we report that cell lines transfected with Bcl-2 paradoxically exhibit increased rates of mitochondrial H2O2 generation. Using isolated mitochondria, we determined that increased H2O2 release results from the oxidation of reduced nicotinamide adenine dinucleotide-linked substrates. Antiapoptotic Bcl-2 family proteins Bcl-xL and Mcl-1 also increase mitochondrial H2O2 release when overexpressed. Chronic exposure of cells to low levels of the mitochondrial uncoupler carbonyl cyanide 4-(triflouromethoxy)phenylhydrazone reduced the rate of H2O2 production by Bcl-xL overexpressing cells, resulting in a decreased ability to remove exogenous H2O2 and enhanced cell death under conditions of acute oxidative stress. Our results indicate that chronic and mild elevations in H2O2 release from Bcl-2, Bcl-xL, and Mcl-1 overexpressing mitochondria lead to enhanced cellular antioxidant defense and protection against death caused by acute oxidative stress. (C) 2004 Elsevier Inc. All rights reserved.
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