Protective roles for ATM in cellular response to oxidative stress

ATM (ataxia telangiectasia mutated), the gene mutated in ataxia telangiecta sia, is related to a family of large phosphatidylinositol 3-kinase domain-c ontaining proteins involved in cell cycle control and DNA repair. We found that ATM(-/-) DT40 cells were more susceptible than mild-type cells to apop tosis induced not only by ionizing radiation and bleomycin but also by non- DNA-damaging apoptotic stimuli such as C-2-ceramide, Furthermore, the apopt osis induced by C-2-ceramide and H2O2 was blocked by anti-oxidants, indicat ing that the ATM(-/-) DT40 cells had a heightened susceptibility to apoptos is induced by reactive oxygen intermediates (ROI), presumably due to defect ive 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 indic ate that ATM plays important roles in the maintenance of the cell homeostas is in response to oxidative damage. (C) 2000 Federation of European Biochem ical Societies.