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ARL15 overexpression attenuates high glucose-induced impairment of insulin signaling and oxidative stress in human umbilical vein endothelial cells.

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机构: [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China [2]Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China [3]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China [4]Department of Laboratory Medicine, National Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610000, China
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关键词: ARL15 HUVEC NO Oxidative stress High glucose

摘要:
Endothelial dysfunction (ED) plays a pivotal role in the development and progression of cardiovascular disease. Recently, genomic studies have found that ARL15, and some of its common genetic variants are associated with type 2 diabetes and coronary atherosclerosis. Since, the function of ARL15 is unclear we aimed at investigating the role of ARL15 in ED induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs). Quantitative real-time PCR was used to access the mRNA expression of ARL15. After exposure to different glucose media, nitric oxide (NO) production and the levels of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) were studied. The underlying signaling pathway was also examined by western blot. Up-regulation of ARL15 attenuates HG-induced impairment in HUVECs. With insulin-stimulation, NO production and the active phosphorylation of the IR/IRS1/AKT/eNOS pathway were significantly increased. ARL15 overexpression was found to decrease the ROS and MDA production and increase SOD level. It could also reduce ERK1/2-Thr183-Tyr185 phosphorylation, NOX2 and NOX4 expression in HG medium. These results suggest that ARL15 could significantly alleviate the dysfunction of HUVECs induced by HG. Our findings help to identify new potential protective effects of ARL15 in HG-induced endothelial impairment. Copyright © 2019 Elsevier Inc. All rights reserved.

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出版当年[2019]版:
大类 | 3 区 医学
小类 | 3 区 医学:研究与实验 3 区 药学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 医学:研究与实验 2 区 药学
第一作者:
第一作者机构: [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China [2]Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China [3]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China
通讯作者:
通讯机构: [1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha 410008, China [2]Hunan Key Laboratory of Pharmacogenetics, Institute of Clinical Pharmacology, Central South University, Changsha 410078, China [3]National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, China [*1]Department of Clinical Pharmacology, Xiangya Hospital, Central South University, 110 Xiangya Rode, Kaifu District, Changsha, Hunan 410008, China
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