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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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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 |
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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 |
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