The protective role of glutathione peroxidase in apoptosis induced by reactive oxygen species.
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 hydroperoxide 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 H202. 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.
Kayanoki
Y
Y
Department of Biochemistry, Osaka University Medical School.
Fujii
J
J
Islam
K N
KN
Suzuki
K
K
Kawata
S
S
Matsuzawa
Y
Y
Taniguchi
N
N
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001555:Benzene Derivatives / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D002460:Cell Line; D002470:Cell Survival; D002994:Clofibrate / Q000494:pharmacology; D005949:Glucose Oxidase / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D010545:Peroxides / Q000032:analysis / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000494:pharmacology*; D020887:Selenious Acid; D012643:Selenium / Q000494:pharmacology / Q000502:physiology; D018036:Selenium Compounds / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides; D014812:Vitamin K / Q000494:pharmacology; D014969:Xanthine Oxidase / Q000494:pharmacology
D000975:Antioxidants; D001555:Benzene Derivatives; D010545:Peroxides; D017382:Reactive Oxygen Species; D018036:Selenium Compounds; D013481:Superoxides; D014812:Vitamin K; D006861:Hydrogen Peroxide; D005949:Glucose Oxidase; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase; D020887:Selenious Acid; D012643:Selenium; D002994:Clofibrate; C007164:cumene hydroperoxide