Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress

The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examin...

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Main Authors: Qunye Zhang, Fan Jiang, Peili Bu, Yun Zhang, Xi Wang, Xiao Wu, Junni Liu
Format: Article
Language:English
Published: MDPI AG 2013-03-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:http://www.mdpi.com/1422-0067/14/3/5633
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author Qunye Zhang
Fan Jiang
Peili Bu
Yun Zhang
Xi Wang
Xiao Wu
Junni Liu
author_facet Qunye Zhang
Fan Jiang
Peili Bu
Yun Zhang
Xi Wang
Xiao Wu
Junni Liu
author_sort Qunye Zhang
collection DOAJ
description The NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress. We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network. These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down. Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells. These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1. Our results may provide a basis for future studies aiming to dissect the specific signaling pathway(s) that mediates specific Sirt2 functions in endothelial cells.
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spelling doaj.art-e724d0cf917243ffbd38142def37adc22022-12-22T03:10:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672013-03-011435633564910.3390/ijms14035633Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative StressQunye ZhangFan JiangPeili BuYun ZhangXi WangXiao WuJunni LiuThe NAD+-dependent deacetylases Sirt1 and Sirt2 mediate cellular stress responses and are highly expressed in vascular endothelial cells. In contrast to the well-documented protective actions of Sirt1, the role of endothelial Sirt2 remains unknown. Using cDNA microarray and PCR validation, we examined global gene expression changes in response to Sirt2 knock down in primary human umbilical vein endothelial cells under oxidative stress. We found that Sirt2 knock down changed expression of 340 genes, which are mainly involved in cellular processes including actin binding, cellular amino acid metabolic process, transmembrane receptor protein serine/threonine kinase signaling, ferrous iron transport, protein transport and localization, cell morphogenesis, and functions associated with endosome membrane and the trans-Golgi network. These genes and associated functions were largely non-overlapping with those altered by Sirt1 knock down. Moreover, we showed that pharmacological inhibition of Sirt2 attenuated oxidant-induced cell toxicity in endothelial cells. These suggest that Sirt2 is functionally important in endothelial cells under oxidative stress, and may have a primarily distinct role as compared to Sirt1. Our results may provide a basis for future studies aiming to dissect the specific signaling pathway(s) that mediates specific Sirt2 functions in endothelial cells.http://www.mdpi.com/1422-0067/14/3/5633Sirt1Sirt2endothelial celloxidative stressfunctional genomicsmicroarray
spellingShingle Qunye Zhang
Fan Jiang
Peili Bu
Yun Zhang
Xi Wang
Xiao Wu
Junni Liu
Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
International Journal of Molecular Sciences
Sirt1
Sirt2
endothelial cell
oxidative stress
functional genomics
microarray
title Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
title_full Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
title_fullStr Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
title_full_unstemmed Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
title_short Global Gene Expression Profiling Reveals Functional Importance of Sirt2 in Endothelial Cells under Oxidative Stress
title_sort global gene expression profiling reveals functional importance of sirt2 in endothelial cells under oxidative stress
topic Sirt1
Sirt2
endothelial cell
oxidative stress
functional genomics
microarray
url http://www.mdpi.com/1422-0067/14/3/5633
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