Cargando…

Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6

Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic r...

Descripción completa

Detalles Bibliográficos
Autores principales: Liu, Rong, Liu, Hua, Ha, Yonju, Tilton, Ronald G., Zhang, Wenbo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138737/
https://www.ncbi.nlm.nih.gov/pubmed/25162034
http://dx.doi.org/10.1155/2014/902842
_version_ 1782331276125011968
author Liu, Rong
Liu, Hua
Ha, Yonju
Tilton, Ronald G.
Zhang, Wenbo
author_facet Liu, Rong
Liu, Hua
Ha, Yonju
Tilton, Ronald G.
Zhang, Wenbo
author_sort Liu, Rong
collection PubMed
description Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H(2)O(2) treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H(2)O(2) treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated) retinoblastoma (Rb) protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H(2)O(2). In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy.
format Online
Article
Text
id pubmed-4138737
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Hindawi Publishing Corporation
record_format MEDLINE/PubMed
spelling pubmed-41387372014-08-26 Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6 Liu, Rong Liu, Hua Ha, Yonju Tilton, Ronald G. Zhang, Wenbo Biomed Res Int Research Article Accumulating evidence has shown that diabetes accelerates aging and endothelial cell senescence is involved in the pathogenesis of diabetic vascular complications, including diabetic retinopathy. Oxidative stress is recognized as a key factor in the induction of endothelial senescence and diabetic retinopathy. However, specific mechanisms involved in oxidative stress-induced endothelial senescence have not been elucidated. We hypothesized that Sirt6, which is a nuclear, chromatin-bound protein critically involved in many pathophysiologic processes such as aging and inflammation, may have a role in oxidative stress-induced vascular cell senescence. Measurement of Sirt6 expression in human endothelial cells revealed that H(2)O(2) treatment significantly reduced Sirt6 protein. The loss of Sirt6 was associated with an induction of a senescence phenotype in endothelial cells, including decreased cell growth, proliferation and angiogenic ability, and increased expression of senescence-associated β-galactosidase activity. Additionally, H(2)O(2) treatment reduced eNOS expression, enhanced p21 expression, and dephosphorylated (activated) retinoblastoma (Rb) protein. All of these alternations were attenuated by overexpression of Sirt6, while partial knockdown of Sirt6 expression by siRNA mimicked the effect of H(2)O(2). In conclusion, these results suggest that Sirt6 is a critical regulator of endothelial senescence and oxidative stress-induced downregulation of Sirt6 is likely involved in the pathogenesis of diabetic retinopathy. Hindawi Publishing Corporation 2014 2014-08-05 /pmc/articles/PMC4138737/ /pubmed/25162034 http://dx.doi.org/10.1155/2014/902842 Text en Copyright © 2014 Rong Liu et al. https://creativecommons.org/licenses/by/3.0/ 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
Liu, Rong
Liu, Hua
Ha, Yonju
Tilton, Ronald G.
Zhang, Wenbo
Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
title Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
title_full Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
title_fullStr Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
title_full_unstemmed Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
title_short Oxidative Stress Induces Endothelial Cell Senescence via Downregulation of Sirt6
title_sort oxidative stress induces endothelial cell senescence via downregulation of sirt6
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4138737/
https://www.ncbi.nlm.nih.gov/pubmed/25162034
http://dx.doi.org/10.1155/2014/902842
work_keys_str_mv AT liurong oxidativestressinducesendothelialcellsenescenceviadownregulationofsirt6
AT liuhua oxidativestressinducesendothelialcellsenescenceviadownregulationofsirt6
AT hayonju oxidativestressinducesendothelialcellsenescenceviadownregulationofsirt6
AT tiltonronaldg oxidativestressinducesendothelialcellsenescenceviadownregulationofsirt6
AT zhangwenbo oxidativestressinducesendothelialcellsenescenceviadownregulationofsirt6