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Glutathione peroxidase‐1 gene knockout on body antioxidant defense in mice
Author(s) -
Lei Xin Gen
Publication year - 2001
Publication title -
biofactors
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.204
H-Index - 94
eISSN - 1872-8081
pISSN - 0951-6433
DOI - 10.1002/biof.5520140113
Subject(s) - gpx1 , oxidative stress , gpx4 , chemistry , antioxidant , knockout mouse , glutathione , glutathione peroxidase , gene knockout , diquat , paraquat , endocrinology , biochemistry , medicine , enzyme , biology , catalase , gene
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.