Affiliation:
1. Department of Key Laboratory of Cardiovascular and Cerebrovascular Drug Research of Liaoning Province, Jinzhou Medical University, Jinzhou 121001, China.
2. Department of Internal Medicine-Cardiovascular, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou 121001, China.
Abstract
Klotho protein secreted in the blood could act as a hormone to regulate various target organs and have a protective effect on the cardiovascular system. Numerous studies had shown that Klotho protein had antioxidative stress, anti-inflammatory, and antiapoptotic effects on vascular endothelial cells. The purpose of this study was to investigate the protective mechanism of Klotho protein on oxidative damage of vascular endothelial cells induced by H2O2. Klotho protein significantly enhanced human umbilical vein endothelial cells viability and increased the activities of antioxidant enzymes (superoxide dismutase, catalase, and heme oxygenase-1 (HO-1)), scavenged reactive oxygen species, and inhibited tumor necrosis factor alpha and interleukin 6 secretion. Klotho protein also reduced the rate of apoptosis of cells and improved the function of vascular endothelial cells (increased nitric oxide secretion). Klotho protein activated nuclear translocation of Nrf2 and increased HO-1 expression. Klotho protein also activated phosphorylation of protein kinase B (AKT), whereas the addition of LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase (PI3K), blocked Klotho-protein-induced Nrf2/HO-1 activation and cytoprotection. Klotho protein enhanced the antioxidant defense ability of the cells by activating the PI3K/AKT pathway, which upregulated the expression of Nrf2/HO-1, thereby inhibiting H2O2-induced oxidative damage.
Publisher
Canadian Science Publishing
Subject
Physiology (medical),Pharmacology,General Medicine,Physiology
Cited by
47 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献