Glutathione peroxidase-1 gene knockout on body antioxidant defense in mice.
To determine the in vivo role of cellular glutathione peroxidase (E.C.1.11.1.9, GPX1), we challenged the GPX1 knockout [GPX1(-/-)], the GPX1 overexpressing [GPX1(+)], and their respective wild-type (WT) mice of different Se and vitamin E status with acute oxidative stress. After these mice were injected with pro-oxidants paraquat or diquat at 12 to 125 mg/kg of body weight, their survival rate and time were a function of their GPX1 activity levels. The GPX1 protection was associated with attenuation of NADPH and NADH oxidation, protein carbonyl and F(2)-isoprostanes formation, and alanine transaminase release in various tissues, and was irreplaceable by high levels of dietary vitamin E or other selenoproteins. The GPX1 expression was also protective against moderate oxidative stress induced by low levels of paraquat or diquat, particularly in the Se-deficient mice. Alteration of GPX1 expression showed no impact on the expression of other selenoproteins and antioxidant enzymes in unstressed mice. Total Se content in liver of the Se-adequate GPX1(-/-) mice was reduced by 60% the WT controls. In conclusion, normal expression of GPX1 is essential and overexpression of GPX1 is beneficial to protect mice against acute oxidative stress.
Lei
X G
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Department of Animal Science, Cornell University, Ithaca, NY 14853, USA. XL20@cornell.edu
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology*; D011506:Proteins / Q000378:metabolism; D012643:Selenium / Q000378:metabolism; D051140:Selenoproteins; D014810:Vitamin E / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D011506:Proteins; D051140:Selenoproteins; D009243:NAD; D014810:Vitamin E; D009249:NADP; D005979:Glutathione Peroxidase; D012643:Selenium; D000094765:Glutathione Peroxidase GPX1; C000722068:Gpx1 protein, mouse