J. Biochem, 1996, Vol. 119, No. 4 817-822
© 1996 Japanese Biochemical Society
research-article |
The Protective Role of Glutathione Peroxidase in Apoptosis Induced by Reactive Oxygen Species1
*Department of Biochemistry Osaka University Medical School 2-2 Yamadaoka, Suita, Osaka 565
Second Department of Internal Medicine, Osaka University Medical School 2-2 Yamadaoka, Suita, Osaka 565
2To whom correspondence should be.addressed.
Selenium-dependent glutathione peroxidase (GPx) plays a protective role in oxidative stress-induced apoptosis. In this study, we demonstrated that MDBK cells, a bovine renal epithelial cell line, exhibited internucleosomal DNA fragmentation characteristic of apoptotic cell death under selenium-deficient conditions with lower doses of hydrogen peroxide (H2O2) than under selenium-supplemented ones. This was due to a decreased amount of GPx in the cells under selenium-deficient conditions, because other antioxidative enzyme activities were not affected by the selenium supplementation. Cumene hydroperox-ide also induced DNA fragmentation in selenium-deficient cells but no ladder formation was observed. Flow cytometric analysis showed that selenium-deficient cells were less capable of scavenging intracellular peroxides after exposure to exogenous H2O2 than selenium-supplemented ones. In contrast, there was no difference in viability between selenium-supplemented and non-supplemented cells in cell survival after exposure to menadione,which activates the electron transport system and increases intracellular superoxide radicals. Clofibrate, a peroxisomal proliferator and an inducer of catalase (CAT), partially protected both Se-deficient and Se-supplemented cells from exogenous H2O2. We concluded that selenium-deficient cells were more easily brought to apoptotic cell death by peroxides, but not by superoxide radicals, than selenium-supplemented ones and that CAT could compensate for the depletion of GPx to a certain degree by scavenging H2O2.
1This work was supported in part by a Grant-in-Aid for Scientific Research on Priority Areas and Specific Project Research on Cancer Bio-Science from the Ministry of Education, Science and Culture of Japan.
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