TY - JOUR
T1 - Protective roles for ATM in cellular response to oxidative stress
AU - Takao, Noriaki
AU - Li, Yingzhu
AU - Yamamoto, Ken Ichi
N1 - Funding Information:
We thank J. Yodoi, N. Taniguchi, M. Inoue and E. Niki for discussion. This work is supported in part by Grants-in-Aid from the Ministry of Education, Science and Culture of Japan.
PY - 2000/4/21
Y1 - 2000/4/21
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Ataxia telangiectasia mutated
KW - Gene targeting
KW - Reactive oxygen intermediate
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U2 - 10.1016/S0014-5793(00)01422-8
DO - 10.1016/S0014-5793(00)01422-8
M3 - Article
C2 - 10781820
AN - SCOPUS:0034697333
VL - 472
SP - 133
EP - 136
JO - FEBS Letters
JF - FEBS Letters
SN - 0014-5793
IS - 1
ER -