Affiliations: Department of Animal Science, Cornell University,
Ithaca, NY 14853, USA
Note: [] PhD, Associate Professor, Department of Animal Science, Morrison
Hall 252, Cornell University, Ithaca, NY 14853, USA. Tel.: +1 607 254 4703;
Fax: +1 607 255 9829; E-mail: XL20@cornell.edu
Abstract: 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.
