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

Osamu Sakai; Toshinori Yasuzawa; Yoshie Sumikawa; Takashi Ueta; Hirotaka Imai; Akiyoshi Sawabe; Shigeru Ueshima

doi:10.1016/j.pathophys.2016.11.002

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

Pathophysiology. 2017 Mar;24(1):9-15. doi: 10.1016/j.pathophys.2016.11.002. Epub 2016 Dec 1.

Authors

Osamu Sakai¹, Toshinori Yasuzawa², Yoshie Sumikawa³, Takashi Ueta⁴, Hirotaka Imai⁵, Akiyoshi Sawabe³, Shigeru Ueshima⁶

Affiliations

¹ Senju Laboratory, Senju Pharmaceutical Co., Ltd., Kobe, Japan.
² Department of Food Science and Nutrition, Faculty of Agriculture, Kindai University, Nara, Japan.
³ Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, Nara, Japan.
⁴ Department of Ophthalmology, Graduate School of Medicine and Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
⁵ School of Pharmaceutical Sciences, Kitasato University, Tokyo, Japan.
⁶ Department of Food Science and Nutrition, Faculty of Agriculture, Kindai University, Nara, Japan; Department of Applied Biological Chemistry, Graduate School of Agriculture, Kindai University, Nara, Japan; Antiaging Centre, Kindai University, Higashi-osaka, Japan. Electronic address: sueshima@nara.kindai.ac.jp.

PMID: 27964880
DOI: 10.1016/j.pathophys.2016.11.002

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 ferroptosis on cell death induced by GPx4 loss in human vascular endothelial cells. In addition, we examined the compensatory activity of brown rice on GPx4 ablation condition. Human umbilical vein endothelial cells were transfected with GPx4 or scramble control siRNA. GPx4 knockdown 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 GPx4 knockdown. Furthermore, ferrostatin-1, inhibitor of ferroptosis, also prevented cytotoxicity and delay of proliferation. In conclusion, our data demonstrated that GPx4 is an essential antioxidant enzyme for protecting lipid peroxidation, and is a regulator of ferroptosis in vascular endothelial cells. Furthermore, vitamin E rich food, such as brown rice, can compensate for GPx4 loss by protecting cells against lipid peroxidation.

Keywords: GPx4; Lipid peroxidation; Oxidative stress; Vascular endothelial cells; Vitamin E.