Protective roles for ATM in cellular response to oxidative stress.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Takao N,Li Y,Yamamoto K

doi

10.1016/s0014-5793(00)01422-8

keywords:

subject

Has Abstract

pub_date

2000-04-21 00:00:00

pages

133-6

issue

1

eissn

0014-5793

issn

1873-3468

pii

S0014579300014228

journal_volume

472

pub_type

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