Protective roles for ATM in cellular response to oxidative stress

FEBS Letters

Yamamoto, Ken-ichi¹  Takao, Noriaki¹  Li, Yingzhu¹ 

[1] Department of Molecular Pathology, Cancer Research Institute, Kanazawa University, Kanazawa 920-0934, Japan

关键词: Reactive oxygen intermediate;    Apoptosis;    Ataxia telangiectasia mutated;    Gene targeting;    A-T;    ataxia telangiectasia;    ATM;    ataxia telangiectasia mutated;    DSB;    double-stranded break;    IR;    ionizing radiation;    PI;    phosphatidylinositol;    ROI;    reactive oxygen intermediates;   

DOI  :  10.1016/S0014-5793(00)01422-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

ATM (ataxia telangiectasia mutated), the gene mutated in ataxia telangiectasia, is related to a family of large phosphatidylinositol 3-kinase domain-containing proteins involved in cell cycle control and DNA repair. We found that ATM^−/− DT40 cells were more susceptible than wild-type cells to apoptosis induced not only by ionizing radiation and bleomycin but also by non-DNA-damaging apoptotic stimuli such as C₂-ceramide. Furthermore, the apoptosis induced by C₂-ceramide and H₂O₂ was blocked by anti-oxidants, indicating that the ATM^−/− DT40 cells had a heightened susceptibility to apoptosis induced by reactive oxygen intermediates (ROI), presumably due to defective ROI-detoxification activities. In support of this hypothesis, we found that more ROI were generated in ATM^−/− DT40 cells than in wild-type cells, following treatment with the above apoptotic stimuli. These results indicate that ATM plays important roles in the maintenance of the cell homeostasis in response to oxidative damage.

【 授权许可】

Unknown