Selenium-dependent cellular glutathione peroxidase protects mice against a pro-oxidant-induced oxidation of NADPH, NADH, lipids, and protein.
Since our prior work indicated that Se-dependent cellular glutathione peroxidase (GPX1) was necessary for protection against paraquat lethality, the present studies were to elucidate the biochemical mechanisms related to that protection. Four groups of mice [Se-deficient or -adequate GPX1 knockout and wild-type (WT)] were injected (i.p.) with 50 mg paraquat/kg body weight and tissues were collected 0, 0.5, 1, 2, 3, or 4 h after the injection. Whereas the ratios of NADPH/NADP and NADH/NAD in lung were reduced by 50-70% only 0.5 h after the injection in all groups, these two ratios in liver of the Se-adequate WT were significantly higher than those of the three GPX1 knockout or deficient groups 2-4 h after the injection. The paraquat-induced pulmonary lipid peroxidation and hepatic protein oxidation, measured as F(2)-isoprostanes and carbonyl contents, respectively, peaked at 1 h in these three groups. No such oxidative events were shown in any tissue of the Se-adequate WT throughout the time course. Whereas the F(2)-isoprostane formation was accelerated by both GPX1 knockout and Se deficiency in liver, it was not significantly elevated by the paraquat treatment in brain of any group. The paraquat injection also resulted in temporal changes in lung GPX activity and GPX1 protein in the Se-adequate WT, and significant reductions in lung total SOD activity in the GPX1 knockout or deficient groups. In conclusion, GPX1 plays a critical role in maintaining the redox status of mice under acute oxidative stress, and protects against paraquat-induced oxidative destruction of lipids and protein in vivo. These protections of GPX1 seem to be inducible and coordinated with those of other antioxidant enzymes.
Cheng
W
W
Department of Animal Science, Cornell University, Ithaca, New York 14853, USA.
Fu
Y X
YX
Porres
J M
JM
Ross
D A
DA
Lei
X G
XG
D000818:Animals; D005979:Glutathione Peroxidase / Q000502:physiology*; D006540:Herbicides / Q000633:toxicity; D015227:Lipid Peroxidation; D051379:Mice; D018345:Mice, Knockout; D009243:NAD / Q000378:metabolism*; D009249:NADP / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010269:Paraquat / Q000633:toxicity; D011506:Proteins / Q000378:metabolism*
D006540:Herbicides; D011506:Proteins; D009243:NAD; D009249:NADP; D005979:Glutathione Peroxidase; D010269:Paraquat