ABSTRACT

This chapter highlights the fundamental cellular processes that are regulated by Glutathione peroxidase 1 (GPx1) in mammalian cells and discusses how the actions of GPx1 on the cellular redox state regulate disease processes. GPx1 is the first member of the Glutathione peroxidase family discovered and is one of the selenium-dependent enzymes of this family of antioxidant enzymes. The suppressive effect of GPx1 overexpression on signal transduction can be mimicked by overexpression of catalase, confirming that hydrogen peroxide is necessary for the signaling events. GPx1 deficiency has been shown to cause pro-atherogenic activation of vascular endothelial cells to augment the development of atherosclerosis. In aging mice, GPx1 deficiency was found to affect aortic function by both endothelium-dependent and endothelium-independent mechanisms, implicating smooth muscle cell dysfunction along with endothelial dysfunction in the abnormal vasodilatory responses. Consistent with the protective effect of GPx1 in cardiac ischemia–reperfusion injury, GPx1 is also protective against ischemia–reperfusion injury in the brain.