| First Author | Fu Y | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 46 | Pages | 43004-9 |
| PubMed ID | 11562367 | Mgi Jnum | J:72598 |
| Mgi Id | MGI:2153292 | Doi | 10.1074/jbc.M106946200 |
| Citation | Fu Y, et al. (2001) Opposite Roles of Selenium-dependent Glutathione Peroxidase-1 in Superoxide Generator Diquat- and Peroxynitrite-induced Apoptosis and Signaling. J Biol Chem 276(46):43004-9 |
| abstractText | 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. |
