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

BACKGROUND: Endothelial 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 mecha...

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Autores principales: Zhou, Xi, Yang, Jining, Zhou, Min, Zhang, Yu, Liu, Yang, Hou, Pengfei, Zeng, Xianglong, Yi, Long, Mi, Mantian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604179/
https://www.ncbi.nlm.nih.gov/pubmed/31303889
http://dx.doi.org/10.1186/s12986-019-0371-6
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author Zhou, Xi
Yang, Jining
Zhou, Min
Zhang, Yu
Liu, Yang
Hou, Pengfei
Zeng, Xianglong
Yi, Long
Mi, Mantian
author_facet Zhou, Xi
Yang, Jining
Zhou, Min
Zhang, Yu
Liu, Yang
Hou, Pengfei
Zeng, Xianglong
Yi, Long
Mi, Mantian
author_sort Zhou, Xi
collection PubMed
description BACKGROUND: Endothelial 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. METHODS: HUVECs 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. RESULTS: RSV 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. CONCLUSIONS: In HUVECs, RSV attenuates endothelial oxidative injury by inducing autophagy in a TFEB-dependent manner.
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spelling pubmed-66041792019-07-12 Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB Zhou, Xi Yang, Jining Zhou, Min Zhang, Yu Liu, Yang Hou, Pengfei Zeng, Xianglong Yi, Long Mi, Mantian Nutr Metab (Lond) Research BACKGROUND: Endothelial 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. METHODS: HUVECs 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. RESULTS: RSV 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. CONCLUSIONS: In HUVECs, RSV attenuates endothelial oxidative injury by inducing autophagy in a TFEB-dependent manner. BioMed Central 2019-07-02 /pmc/articles/PMC6604179/ /pubmed/31303889 http://dx.doi.org/10.1186/s12986-019-0371-6 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Zhou, Xi
Yang, Jining
Zhou, Min
Zhang, Yu
Liu, Yang
Hou, Pengfei
Zeng, Xianglong
Yi, Long
Mi, Mantian
Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB
title Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB
title_full Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB
title_fullStr Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB
title_full_unstemmed Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB
title_short Resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor EB
title_sort resveratrol attenuates endothelial oxidative injury by inducing autophagy via the activation of transcription factor eb
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6604179/
https://www.ncbi.nlm.nih.gov/pubmed/31303889
http://dx.doi.org/10.1186/s12986-019-0371-6
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