Role of GPx4 in human vascular endothelial cells, and the compensatory activity of brown rice on GPx4 ablation condition

Abstract Oxidative stress is implicated in the pathologies of vascular endothelial cells. However, the importance of specific antioxidant enzymes in vascular endothelial cells is not fully understood. The purpose of this study was to elucidate the importance of Glutathione peroxidase 4 ( GPx4), and the involvement of ferroptosison cell death induced by GPx4loss in human vascular endothelial cells. In addition, we examined the compensatory activity of brown rice on GPx4ablation condition. Human umbilical vein endothelial cellswere transfected with GPx4or scramble control siRNA. GPx4knockdown caused the increase in the levels of lipid oxidation, and induced cytotoxicity. On the other hand, α-tocopherol (vitamin E) and extract of brown rice, ameliorated lipid peroxidation, cytotoxicity, and delay of proliferation induced by GPx4knockdown. Furthermore, ferrostatin-1, inhibitor of ferroptosis, also prevented cytotoxicity and delay of proliferation. In conclusion, our data demonstrated that GPx4is an essential antioxidant enzyme for protecting lipid peroxidation, and is a regulator of ferroptosisin vascular endothelial cells. Furthermore, vitamin E rich food, such as brown rice, can compensate for GPx4loss by protecting cells against lipid peroxidation.