Mice with a homozygous null mutation for the most abundant glutathione peroxidase, Gpx1, show increased susceptibility to the oxidative stress-inducing agents paraquat and hydrogen peroxide.
JB de Haan, C Bladier, P Griffiths, M Kelner, RD O'Shea, NS Cheung, RT Bronson, MJ Silvestro, S Wild, SS Zheng, PM Beart, PJ Hertzog, I Kola
Journal of Biological Chemistry | Published : 1998
Glutathione peroxidases have been thought to function in cellular antioxidant defense. However, some recent studies on Gpx1 knockout (-/-) mice have failed to show a role for Gpx1 under conditions of oxidative stress such as hyperbaric oxygen and the exposure of eye lenses to high levels of H2O2. These findings have, unexpectedly, raised the issue of the role of Gpx1, especially under conditions of oxidative stress. Here we demonstrate a role for Gpx1 in protection against oxidative stress by showing that Gpx1 (-/-) mice are highly sensitive to the oxidant paraquat. Lethality was already detected within 24 h in mice exposed to paraquat at 10 mg.kg-1 (approximately (1)/(7) the LD50 of wild-ty..View full abstract