New roles of glutathione peroxidase-1 in oxidative stress and diabetes

Abstract

Glutathione peroxidase-1 (GPX1) was identified as an antioxidant enzyme in 1957 and as a selenoprotein in 1972. In the last ten years, ample data have been generated from several lines of GPX1 knockout mice, showing an essential role of GPX1 in defending against severe oxidative stress mediated by pro-oxidants. This protection is associated with attenuated oxidation of NADPH, NADH, lipid, and protein. When Sedeficient mice are under mild oxidative stress, minute amounts of GPX1 activity in tissues are able to protect them against the pro-oxidant-induced lethality and hepatic aponecrosis. Strikingly, GPX1 prevents apoptosis of hepatocytes caused by reactive oxygen species, but potentiates cell death caused by reactive nitrogen species. Mice overexpressing GPX1 developed insulin resistance and obesity. These new data illustrate mixed roles of GPX1 in coping with different types of oxidative stress, and suggest a possible deleterious impact of GPX1 up-regulation on glucose metabolism.