Protective roles for ATM in cellular response to oxidative stress

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 mild-type cells to apoptosis induced not only by ionizing radiation and bleomycin but also by non-DNA-damaging apoptotic stimuli such as C-2-ceramide, Furthermore, the apoptosis induced by C-2-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. (C) 2000 Federation of European Biochemical Societies.