The Protective Role of Glutathione Peroxidase in Apoptosis Induced by Reactive Oxygen Species

• Published in: Journal of biochemistry (Tokyo) 1996-04, Vol.119 (4), p.817-822
• Main Authors: Kayanoki, Yoshiro, Fujii, Junichi, Islam, Kazi Nazrul, Suzuki, Keiichiro, Kawata, Sumio, Matsuzawa, Yuji, Taniguchi, Naoyuki
• Format: Article
• Language: English
• Subjects: Animals; Antioxidants - pharmacology; apoptosis; Apoptosis - drug effects; Apoptosis - physiology; Benzene Derivatives - pharmacology; catalase; Catalase - metabolism; Cattle; Cell Line; Cell Survival; Clofibrate - pharmacology; Glucose Oxidase - pharmacology; glutathione peroxidase; Glutathione Peroxidase - physiology; hydrogen peroxide; Hydrogen Peroxide - pharmacology; Oxidative Stress; Peroxides - analysis; Peroxides - pharmacology; Reactive Oxygen Species - pharmacology; Selenious Acid; Selenium - pharmacology; Selenium - physiology; Selenium Compounds - pharmacology; selenium deficiency; Superoxide Dismutase - metabolism; Superoxides; Vitamin K - pharmacology; Xanthine Oxidase - pharmacology
• ISSN: 0021-924X
• DOI: 10.1093/oxfordjournals.jbchem.a021313

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.