Klotho ameliorates oxidized low density lipoprotein (ox-LDL)-induced oxidative stress via regulating LOX-1 and PI3K/Akt/eNOS pathways

Lipids in Health and Disease

Research

Chang Liu¹  Yibo Zhang²  Yanbing Wang³  Yansheng Yao³ 

[1] Department of Endocrinology, First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, China;Department of Pathogenic Biology, Jinzhou Medical University, Jinzhou, Liaoning, China;Jinzhou Medical University, Jinzhou, Liaoning, China;

关键词: Klotho;    Oxidized low density lipoprotein;    Oxidative stress;    Lectin-like ox-LDL receptor;    Human umbilical vein endothelial cells;   

DOI  :  10.1186/s12944-017-0447-0

 received in 2016-09-26, accepted in 2017-03-09,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundAtherosclerosis is a common cardiovascular disease that causes myocardial infarction, heart failure, and stroke. Increased oxidized low density lipoprotein (ox-LDL) in the sub-endothelium is the characteristic origin of atherogenesis. Klotho, an anti-aging protein, has been reported to protect against atherosclerosis and ameliorate endothelial dysfunction in vivo. The aim of this study is to investigatethe anti-oxidative activity of Klothoin ox-LDL-treated human umbilical vein endothelial cells (HUVECs).MethodsAfter pre-treatment with 200 pMKlotho for 1 h, HUVECs were stimulated with 50 μg/ml ox-LDL for 24 h. Reactive oxygen species (ROS) and superoxide dismutase (SOD) levels were analyzed in the cells. Nitric oxide (NO) concertation was measured in the medium supernatant. Related proteins or genes were detected with Western blot or real time PCR, respectively, in the cell lysates.ResultsInitially, oxidative damage in HUVECs was established by adding 50 μg/mL ox-LDL, which resulted in decreased cellular viability, SOD/Cu/Zn-SOD and endothelial NO synthase (eNOS) expression and NO production, as well as increased malondialdehyde (MDA) levels, ROS production, inducible NO synthase (iNOS), phosphatidyl inositol-3 kinase (PI3K), protein kinase B (Akt), gp91 phox, and lectin-like ox-LDL receptor (LOX-1) expression in HUVECs. Pre-incubation with recombinant Klotho (200 pM) significantly prevented all of these alterations. These results suggest that Klotho can attenuate ox-LDL-induced oxidative stress in HUVECs through upregulating oxidative scavengers (SOD and NO) viaactivating the PI3K/Akt/eNOS pathway and depressing LOX-1expression.ConclusionsThese results suggest that Klotho has a potential therapeutic effect on attenuating endothelial dysfunction and ameliorating atherosclerosis.

【 授权许可】

CC BY   
© The Author(s). 2017

【 图 表 】

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