|
|
||||||||
Department of Animal Science, Cornell University, Ithaca, New York 14853, USA
1Correspondence: Department of Animal Science, 252 Morrison Hall, Cornell University, Ithaca, NY 14853, USA. E-mail: XL20{at}cornell.edu
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 5070% 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 24 h after the injection. The paraquat-induced pulmonary lipid peroxidation and hepatic protein oxidation, measured as F2-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 F2-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.-H., Fu, Y. X., Porres, J. M., Ross, D. A., Lei, X. G.. Selenium-dependent cellular glutathione peroxidase protects mice against a pro-oxidant-induced oxidation of NADPH, NADH, lipids, and protein.
Key Words: F2-isoprostanes carbonyl knockout antioxidation SOD
This article has been cited by other articles:
![]() |
M. S. Scimeca, D. J. Lisk, T. Prolla, and X. G. Lei Effects of gpx4 Haploid Insufficiency on GPx4 Activity, Selenium Concentration, and Paraquat-Induced Protein Oxidation in Murine Tissues Exp Biol Med, November 1, 2005; 230(10): 709 - 714. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. G. Lei and W.-H. Cheng New Roles for an Old Selenoenzyme: Evidence from Glutathione Peroxidase-1 Null and Overexpressing Mice J. Nutr., October 1, 2005; 135(10): 2295 - 2298. [Abstract] [Full Text] [PDF] |
||||
![]() |
B. M. Berg, J. P. Godbout, J. Chen, K. W. Kelley, and R. W. Johnson {alpha}-Tocopherol and Selenium Facilitate Recovery from Lipopolysaccharide-Induced Sickness in Aged Mice J. Nutr., May 1, 2005; 135(5): 1157 - 1163. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. P. McClung, C. A. Roneker, W. Mu, D. J. Lisk, P. Langlais, F. Liu, and X. G. Lei Development of insulin resistance and obesity in mice overexpressing cellular glutathione peroxidase PNAS, June 15, 2004; 101(24): 8852 - 8857. [Abstract] [Full Text] [PDF] |
||||
![]() |
X. Wang, S. A. Phelan, K. Forsman-Semb, E. F. Taylor, C. Petros, A. Brown, C. P. Lerner, and B. Paigen Mice with Targeted Mutation of Peroxiredoxin 6 Develop Normally but Are Susceptible to Oxidative Stress J. Biol. Chem., June 27, 2003; 278(27): 25179 - 25190. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. N. Reddy, F. J. Giblin, L.-R. Lin, L. Dang, N. J. Unakar, D. C. Musch, D. L. Boyle, L. J. Takemoto, Y.-S. Ho, T. Knoernschild, et al. Glutathione Peroxidase-1 Deficiency Leads to Increased Nuclear Light Scattering, Membrane Damage, and Cataract Formation in Gene-Knockout Mice Invest. Ophthalmol. Vis. Sci., December 1, 2001; 42(13): 3247 - 3255. [Abstract] [Full Text] [PDF] |
||||
![]() |
F Candan and H Alagozlu Captopril inhibits the pulmonary toxicity of paraquat in rats Human and Experimental Toxicology, December 1, 2001; 20(12): 637 - 641. [Abstract] [PDF] |
||||
![]() |
Y. Fu, H. Sies, and X. G. Lei Opposite Roles of Selenium-dependent Glutathione Peroxidase-1 in Superoxide Generator Diquat- and Peroxynitrite-induced Apoptosis and Signaling J. Biol. Chem., November 9, 2001; 276(46): 43004 - 43009. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. A. A. COMHAIR, P. R. BHATHENA, C. FARVER, F. B. J. M. THUNNISSEN, and S. C. ERZURUM Extracellular glutathione peroxidase induction in asthmatic lungs: evidence for redox regulation of expression in human airway epithelial cells FASEB J, January 1, 2001; 15(1): 70 - 78. [Abstract] [Full Text] [PDF] |
||||
![]() |
Y. Fu, W.-H. Cheng, D. A. Ross, and X. g. Lei Cellular Glutathione Peroxidase Protects Mice Against Lethal Oxidative Stress Induced by Various Doses of Diquat Exp Biol Med, November 1, 1999; 222(2): 164 - 169. [Abstract] [Full Text] [PDF] |
||||
![]() |
W.-H. Cheng, B. A. Valentine, and X. G. Lei High Levels of Dietary Vitamin E Do Not Replace Cellular Glutathione Peroxidase in Protecting Mice from Acute Oxidative Stress J. Nutr., November 1, 1999; 129(11): 1951 - 1957. [Abstract] [Full Text] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |