Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB

Nutrition & Metabolism

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[1] 0000 0004 1760 6682, grid.410570.7, Research Center for Nutrition and Food Safety, Chongqing Key Laboratory of Nutrition and Food Safety, Institute of Military Preventive Medicine, Third Military Medical University (Army Medical University), NO.30 Gao Tan Yan Street, Shapingba District, 400038, Chongqing, People’s Republic of China;

关键词: Resveratrol;    TFEB;    Autophagy;    Endothelial cells;    Atherosclerosis;   

DOI  :  10.1186/s12986-019-0371-6

来源: publisher

【 摘 要 】

BackgroundEndothelial oxidative injury is a key event in the pathogenesis of atherosclerosis (AS). Resveratrol (RSV) attenuates the oxidative injury in human umbilical vein endothelial cells (HUVECs). Autophagy is critical for the RSV-induced protective effects. However, the exact underlying mechanisms haven’t been completely elucidated. Thus, we aimed to explore the role of autophagy of the anti-oxidation of RSV and the underlying mechanism in palmitic acid (PA)-stimulated HUVECs.MethodsHUVECs were pretreated with 10 μM of RSV for 2 h and treated with 200 μM of PA for an additional 24 h. Cell viability, intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels were estimated with a microplate reader and confocal microscope. Autophagosomes were analyzed by transmission electron microscopy, while lysosomes by confocal microscopy. The expression of transcription factor EB (TFEB) and related genes were quantified by qRT-PCR assay. Furthermore, TFEB levels, autophagy, and lysosomes were examined by western blot assay.ResultsRSV pretreatment suppressed the PA-induced decline in cell viability and elevation in ROS and MDA levels in HUVECs. RSV pretreatment also increased LC3 production and P62 degradation while promoted the autophagosomes formation. However, 3-methyladenine (3-MA) treatment attenuated RSV-induced autophagy. RSV pretreatment upregulated the TFEB and TFEB-modulated downstream genes expression in a concentration-dependent manner. Additionally, in cells transfected with TFEB small interfering RNA, RSV-induced TFEB expression and subsequent autophagy were abolished. Meanwhile, the TFEB-modulated genes expression, the lysosomes formation and the RSV-induced anti-oxidation were suppressed.ConclusionsIn HUVECs, RSV attenuates endothelial oxidative injury by inducing autophagy in a TFEB-dependent manner.

【 授权许可】

CC BY