Opposite roles of selenium-dependent glutathione peroxidase-1 in superoxide generator diquat- and peroxynitrite-induced apoptosis and signaling

Citation
Yx. Fu et al., Opposite roles of selenium-dependent glutathione peroxidase-1 in superoxide generator diquat- and peroxynitrite-induced apoptosis and signaling, J BIOL CHEM, 276(46), 2001, pp. 43004-43009
Citations number
59
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
46
Year of publication
2001
Pages
43004 - 43009
Database
ISI
SICI code
0021-9258(20011116)276:46<43004:OROSGP>2.0.ZU;2-F
Abstract
Oxidative injuries including apoptosis can be induced by reactive oxygen sp ecies (ROS) and reactive nitrogen species (RNS) in aerobic metabolism. We d etermined impacts of a selenium-dependent glutathione peroxidase-1 (GPX1) o n apoptosis induced by diquat (DQ), a ROS (superoxide) generator, and perox ynitrite (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 P N for up to 12 h. Loss of cell viability, high levels of apoptotic cells, a nd severe DNA fragmentation were produced by DQ in only GPX1-/- cells and b y 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 les s and/or slower cellular GSH depletion was caused by DQ or PN in GPX1-/- th an in WT cells, and corresponding GSSG accumulation occurred only in the la tter. In conclusion, it is most striking that, although GPX1 protects again st apoptosis induced by superoxide-generator DQ, the enzyme actually promot es apoptosis induced by PN in murine hepatocytes. Indeed, GSH is a physiolo gical substrate for GPX1 in coping with ROS in these cells.