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Protective roles for ATM in cellular response to oxidative stress
Author(s) -
Takao Noriaki,
Li Yingzhu,
Yamamoto Ken-ichi
Publication year - 2000
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(00)01422-8
Subject(s) - ataxia telangiectasia , dna damage , apoptosis , microbiology and biotechnology , oxidative stress , reactive oxygen species , ceramide , dna repair , biology , chemistry , dna , biochemistry
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 C 2 ‐ceramide. Furthermore, the apoptosis induced by C 2 ‐ceramide and H 2 O 2 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.