Contribution of mitochondrial DNA repair to cell resistance from oxidative stress

被引:32
作者
Grishko, VI
Rachek, LI
Spitz, DR
Wilson, GL
LeDoux, SP [1 ]
机构
[1] Univ S Alabama, Coll Med, Dept Cell Biol & Neurosci, Mobile, AL 36688 USA
[2] Univ S Alabama, Coll Med, Dept Orthoped, Mobile, AL 36688 USA
[3] Univ Iowa, Free Rad & Radiat Biol Program, Dept Radiat Oncol, Holden Comprehens Canc Ctr, Iowa City, IA 52242 USA
关键词
D O I
10.1074/jbc.M413022200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Numerous studies have revealed that a part of the cellular response to chronic oxidative stress involves increased antioxidant capacity. However, another defense mechanism that has received less attention is DNA repair. Because of the important homeostatic role of mitochondria and the exquisite sensitivity of mitochondrial DNA (mtDNA) to oxidative damage, we hypothesized that mtDNA repair plays an important role in the protection against oxidative stress. To test this hypothesis mtDNA damage and repair was evaluated in normal HA1 Chinese hamster fibroblasts and oxidative stress-resistant variants isolated following chronic exposure to H2O2 or 95% O-2. Reactive oxygen species were generated enzymatically using xanthine oxidase and hypoxanthine. When treated with xanthine oxidase reduced levels of initial mtDNA damage and enhanced mtDNA repair were observed in the cells from the oxidative stress-resistant variants, relative to the parental cell line. This enhanced mtDNA repair correlated with an increase in mitochondrial apurinic/apyrimidinic endonuclease activity in both H2O2- and O-2-resistant HA1 variants. This is the first report showing enhanced mtDNA repair in the cellular response to chronic oxidative stress. These results provide further evidence for the crucial role that mtDNA repair pathways play in protecting cells against the deleterious effects of reactive oxygen species.
引用
收藏
页码:8901 / 8905
页数:5
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