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PMID:11562367
| Citation |
Fu, Y, Sies, H and Lei, XG (2001) Opposite roles of selenium-dependent glutathione peroxidase-1 in superoxide generator diquat- and peroxynitrite-induced apoptosis and signaling. J. Biol. Chem. 276:43004-9 |
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| Abstract |
Oxidative injuries including apoptosis can be induced by reactive oxygen species (ROS) and reactive nitrogen species (RNS) in aerobic metabolism. We determined impacts of a selenium-dependent glutathione peroxidase-1 (GPX1) on apoptosis induced by diquat (DQ), a ROS (superoxide) generator, and peroxynitrite (PN), a potent RNS. Hepatocytes were isolated from GPX1 knockout (GPX1-/-) or wild-type (WT) mice, and treated with 0.5 mm DQ or 0.1-0.8 mm PN for up to 12 h. Loss of cell viability, high levels of apoptotic cells, and severe DNA fragmentation were produced by DQ in only GPX1-/- cells and by PN in only WT cells. These two groups of cells shared similar cytochrome c release, caspase-3 activation, and p21(WAF1/CIP1) cleavage. Higher levels of protein nitration were induced by PN in WT than GPX1-/- cells. Much less and/or slower cellular GSH depletion was caused by DQ or PN in GPX1-/- than in WT cells, and corresponding GSSG accumulation occurred only in the latter. In conclusion, it is most striking that, although GPX1 protects against apoptosis induced by superoxide-generator DQ, the enzyme actually promotes apoptosis induced by PN in murine hepatocytes. Indeed, GSH is a physiological substrate for GPX1 in coping with ROS in these cells. |
| Links |
PubMed Online version:10.1074/jbc.M106946200 |
| Keywords |
Animals; Apoptosis; Blotting, Western; Caspase 3; Caspases/metabolism; Cell Nucleus/metabolism; Cell Survival; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p21; Cyclins/metabolism; Cytochrome c Group/metabolism; Cytosol/metabolism; DNA Fragmentation; Diquat/metabolism; Dose-Response Relationship, Drug; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Glutathione/metabolism; Glutathione Peroxidase/physiology; Hepatocytes; Mice; Mice, Knockout; Mitogen-Activated Protein Kinases/metabolism; Peroxynitrous Acid/metabolism; Protein Binding; Reactive Oxygen Species; Selenium/metabolism; Signal Transduction; Time Factors; p38 Mitogen-Activated Protein Kinases |
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Significance
Annotations
| Gene product | Qualifier | GO ID | GO term name | Evidence Code | with/from | Aspect | Notes | Status |
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