Cargando…

Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1

Oxidized low-density lipoprotein- (Ox-LDL-) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox-LDL-induced endothelium injury. The objective of this study was to determine the mechanisms unde...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhang, Yanlin, Cao, Xueqin, Zhu, Wawa, Liu, Zhihua, Liu, Huihui, Zhou, Yande, Cao, Yongjun, Liu, Chunfeng, Xie, Ying
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812467/
https://www.ncbi.nlm.nih.gov/pubmed/27069532
http://dx.doi.org/10.1155/2016/7589813
_version_ 1782424179798179840
author Zhang, Yanlin
Cao, Xueqin
Zhu, Wawa
Liu, Zhihua
Liu, Huihui
Zhou, Yande
Cao, Yongjun
Liu, Chunfeng
Xie, Ying
author_facet Zhang, Yanlin
Cao, Xueqin
Zhu, Wawa
Liu, Zhihua
Liu, Huihui
Zhou, Yande
Cao, Yongjun
Liu, Chunfeng
Xie, Ying
author_sort Zhang, Yanlin
collection PubMed
description Oxidized low-density lipoprotein- (Ox-LDL-) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox-LDL-induced endothelium injury. The objective of this study was to determine the mechanisms underlying Ox-LDL-induced autophagy dysfunction and RSV-mediated protection in human umbilical vein endothelial cells (HUVECs). The results showed that Ox-LDL suppressed the expression of sirtuin 1 (SIRT1) and increased LC3-II and sequestosome 1 (p62) protein levels without altering p62 mRNA levels in HUVECs. Pretreatment with bafilomycin A1 (BafA1) to inhibit lysosomal degradation abrogated the Ox-LDL-induced increase in LC3-II protein level. Ox-LDL increased colocalization of GFP and RFP puncta in mRFP-GFP-tandem fluorescent LC3- (tf-LC3-) transfected cells. Moreover, Ox-LDL decreased the expression of mature cathepsin D and attenuated cathepsin D activity. Pretreatment with RSV increased the expression of SIRT1 and LC3-II and increased p62 protein degradation. RSV induced RFP-LC3 aggregation more than GFP-LC3 aggregation. RSV restored lysosomal function and promoted Ox-LDL degradation in HUVECs. All the protective effects of RSV were blocked after SIRT1 was knocked down. These findings demonstrated that RSV upregulated the expression of SIRT1, restored lysosomal function, enhanced Ox-LDL-induced impaired autophagic flux, and promoted Ox-LDL degradation through the autophagy-lysosome degradation pathway in HUVECs.
format Online
Article
Text
id pubmed-4812467
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-48124672016-04-11 Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1 Zhang, Yanlin Cao, Xueqin Zhu, Wawa Liu, Zhihua Liu, Huihui Zhou, Yande Cao, Yongjun Liu, Chunfeng Xie, Ying Oxid Med Cell Longev Research Article Oxidized low-density lipoprotein- (Ox-LDL-) induced autophagy dysfunction in human vascular endothelial cells contributes to the development of atherosclerosis (AS). Resveratrol (RSV) protects against Ox-LDL-induced endothelium injury. The objective of this study was to determine the mechanisms underlying Ox-LDL-induced autophagy dysfunction and RSV-mediated protection in human umbilical vein endothelial cells (HUVECs). The results showed that Ox-LDL suppressed the expression of sirtuin 1 (SIRT1) and increased LC3-II and sequestosome 1 (p62) protein levels without altering p62 mRNA levels in HUVECs. Pretreatment with bafilomycin A1 (BafA1) to inhibit lysosomal degradation abrogated the Ox-LDL-induced increase in LC3-II protein level. Ox-LDL increased colocalization of GFP and RFP puncta in mRFP-GFP-tandem fluorescent LC3- (tf-LC3-) transfected cells. Moreover, Ox-LDL decreased the expression of mature cathepsin D and attenuated cathepsin D activity. Pretreatment with RSV increased the expression of SIRT1 and LC3-II and increased p62 protein degradation. RSV induced RFP-LC3 aggregation more than GFP-LC3 aggregation. RSV restored lysosomal function and promoted Ox-LDL degradation in HUVECs. All the protective effects of RSV were blocked after SIRT1 was knocked down. These findings demonstrated that RSV upregulated the expression of SIRT1, restored lysosomal function, enhanced Ox-LDL-induced impaired autophagic flux, and promoted Ox-LDL degradation through the autophagy-lysosome degradation pathway in HUVECs. Hindawi Publishing Corporation 2016 2016-03-16 /pmc/articles/PMC4812467/ /pubmed/27069532 http://dx.doi.org/10.1155/2016/7589813 Text en Copyright © 2016 Yanlin Zhang et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Zhang, Yanlin
Cao, Xueqin
Zhu, Wawa
Liu, Zhihua
Liu, Huihui
Zhou, Yande
Cao, Yongjun
Liu, Chunfeng
Xie, Ying
Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
title Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
title_full Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
title_fullStr Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
title_full_unstemmed Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
title_short Resveratrol Enhances Autophagic Flux and Promotes Ox-LDL Degradation in HUVECs via Upregulation of SIRT1
title_sort resveratrol enhances autophagic flux and promotes ox-ldl degradation in huvecs via upregulation of sirt1
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4812467/
https://www.ncbi.nlm.nih.gov/pubmed/27069532
http://dx.doi.org/10.1155/2016/7589813
work_keys_str_mv AT zhangyanlin resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT caoxueqin resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT zhuwawa resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT liuzhihua resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT liuhuihui resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT zhouyande resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT caoyongjun resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT liuchunfeng resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1
AT xieying resveratrolenhancesautophagicfluxandpromotesoxldldegradationinhuvecsviaupregulationofsirt1