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Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats

Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced ea...

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Autores principales: Zhang, Xiang-Sheng, Wu, Qi, Wu, Ling-Yun, Ye, Zhen-Nan, Jiang, Tian-Wei, Li, Wei, Zhuang, Zong, Zhou, Meng-Liang, Zhang, Xin, Hang, Chun-Hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133967/
https://www.ncbi.nlm.nih.gov/pubmed/27735947
http://dx.doi.org/10.1038/cddis.2016.292
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author Zhang, Xiang-Sheng
Wu, Qi
Wu, Ling-Yun
Ye, Zhen-Nan
Jiang, Tian-Wei
Li, Wei
Zhuang, Zong
Zhou, Meng-Liang
Zhang, Xin
Hang, Chun-Hua
author_facet Zhang, Xiang-Sheng
Wu, Qi
Wu, Ling-Yun
Ye, Zhen-Nan
Jiang, Tian-Wei
Li, Wei
Zhuang, Zong
Zhou, Meng-Liang
Zhang, Xin
Hang, Chun-Hua
author_sort Zhang, Xiang-Sheng
collection PubMed
description Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH.
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spelling pubmed-51339672016-12-16 Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats Zhang, Xiang-Sheng Wu, Qi Wu, Ling-Yun Ye, Zhen-Nan Jiang, Tian-Wei Li, Wei Zhuang, Zong Zhou, Meng-Liang Zhang, Xin Hang, Chun-Hua Cell Death Dis Original Article Increasing evidence indicates that sirtuin 1 (SIRT1) is implicated in a wide range of cellular functions, such as oxidative stress, inflammation and apoptosis. The aim of this study was to investigate the change of SIRT1 in the brain after subarachnoid hemorrhage (SAH) and its role on SAH-induced early brain injury (EBI). In the first set of experiments, rats were randomly divided into sham group and SAH groups at 2, 6, 12, 24, 48 and 72 h. The expression of SIRT1 was evaluated by western blot analysis, immunohistochemistry and immunofluorescence. In another set of experiments, SIRT1-specific inhibitor (sirtinol) and activator (activator 3) were exploited to study the role of SIRT1 in SAH-induced EBI. It showed that the protein level of SIRT1 was markedly elevated at the early stage of SAH and peaked at 24 h after SAH. The expression of SIRT1 could be observed in neurons and microglia, and the enhanced SIRT1 was mainly located in neurons after SAH. Administration of sirtinol inhibited the expression and activation of SIRT1 pathways after SAH, while activator 3 enhanced the expression and activation of SIRT1 pathways after SAH. In addition, inhibition of SIRT1 could exacerbate forkhead transcription factors of the O class-, nuclear factor-kappa B- and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis, leading to aggravated brain injury after SAH. In contrast, activator 3 treatment could reduce forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative damage, neuroinflammation and neuronal apoptosis to protect against EBI. These results suggest that SIRT1 plays an important role in neuroprotection against EBI after SAH by deacetylation and subsequent inhibition of forkhead transcription factors of the O class-, nuclear factor-kappa B-, and p53-induced oxidative, inflammatory and apoptotic pathways. SIRT1 might be a new promising molecular target for SAH. Nature Publishing Group 2016-10 2016-10-13 /pmc/articles/PMC5133967/ /pubmed/27735947 http://dx.doi.org/10.1038/cddis.2016.292 Text en Copyright © 2016 The Author(s) http://creativecommons.org/licenses/by/4.0/ Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Original Article
Zhang, Xiang-Sheng
Wu, Qi
Wu, Ling-Yun
Ye, Zhen-Nan
Jiang, Tian-Wei
Li, Wei
Zhuang, Zong
Zhou, Meng-Liang
Zhang, Xin
Hang, Chun-Hua
Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
title Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
title_full Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
title_fullStr Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
title_full_unstemmed Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
title_short Sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
title_sort sirtuin 1 activation protects against early brain injury after experimental subarachnoid hemorrhage in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5133967/
https://www.ncbi.nlm.nih.gov/pubmed/27735947
http://dx.doi.org/10.1038/cddis.2016.292
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