Contribution of mitochondrial DNA repair to cell resistance from oxidative stress

Valentina I Grishko; Lyudmila I Rachek; Douglas R Spitz; Glenn L Wilson; Susan P LeDoux

doi:10.1074/jbc.M413022200

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Contribution of mitochondrial DNA repair to cell resistance from oxidative stress

Journal article

Open access

Peer reviewed

Contribution of mitochondrial DNA repair to cell resistance from oxidative stress

Valentina I Grishko, Lyudmila I Rachek, Douglas R Spitz, Glenn L Wilson and Susan P LeDoux

The Journal of biological chemistry, Vol.280(10), pp.8901-8905

03/11/2005

DOI: 10.1074/jbc.M413022200

PMID: 15632148

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Abstract

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% O2. 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 O2-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.

Animals

Biomarkers - analysis

Cell Culture Techniques

Cell Line

Cricetinae

Cricetulus

DNA Repair

DNA, Mitochondrial - genetics

Fibroblasts - cytology

Fibroblasts - drug effects

Fibroblasts - physiology

Guanine - analogs & derivatives

Guanine - analysis

Hydrogen Peroxide - pharmacology

Mitochondria - drug effects

Mitochondria - genetics

Mitochondria - physiology

Oxidative Stress - genetics

Oxidative Stress - physiology

Oxygen - pharmacology

Reactive Oxygen Species - pharmacology

Details

Title: Subtitle: Contribution of mitochondrial DNA repair to cell resistance from oxidative stress
Creators: Valentina I Grishko - University of South Alabama
Lyudmila I Rachek - University of South Alabama
Douglas R Spitz - Holden
Glenn L Wilson - University of South Alabama
Susan P LeDoux - University of South Alabama
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.280(10), pp.8901-8905
DOI: 10.1074/jbc.M413022200
PMID: 15632148
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Grant note: ES05865 / NIEHS NIH HHS ES03456 / NIEHS NIH HHS AG19602 / NIA NIH HHS CA100045 / NCI NIH HHS
Language: English
Date published: 03/11/2005
Academic Unit: Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984313087102771

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