SIRT1 suppresses PMA and ionomycin-induced ICAM-1 expression in endothelial cells
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- 作者：YuYan Jia (1)
Peng Gao (1)
HouZao Chen (1)
YanZhen Wan (1)
Ran Zhang (1)
ZhuQin Zhang (1)
RuiFeng Yang (1)
Xu Wang (1)
Jing Xu (1)
DePei Liu (1) - 关键词：SIRT1 ; ICAM ; 1 ; PMA and ionomycin
- 刊名：Science China Life Sciences
- 出版年：2013
- 出版时间：January 2013
- 年：2013
- 卷：56
- 期：1
- 页码：19-25
- 全文大小：693KB
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Peng Gao (1)
HouZao Chen (1)
YanZhen Wan (1)
Ran Zhang (1)
ZhuQin Zhang (1)
RuiFeng Yang (1)
Xu Wang (1)
Jing Xu (1)
DePei Liu (1)
1. State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100005, People’s Republic of China
文摘
Intercellular adhesion molecule-1 (ICAM-1) plays an important role in the recruitment of leukocytes to the endothelium, which causes inflammation and initiation of atherosclerosis. We have previously shown that endothelium-specific over-expression of class III deacetylase SIRT1 decreases atherosclerosis. We therefore addressed the hypothesis that SIRT1 suppresses ICAM-1 expression in the endothelial cells. Here, we found that expression of SIRT1 and ICAM-1 was significantly induced by PMA and ionomycin (PMA/Io) in human umbilical vein endothelial cells (HUVECs). Adenovirus-mediated over-expression of SIRT1 significantly inhibited PMA/Io-induced ICAM-1 expression in HUVECs. Knockdown of SIRT1 by RNA interference (RNAi) resulted in increased expression of ICAM-1 in HUVECs. Luciferase report assay showed that over-expression of SIRT1 suppressed ICAM-1 promoter activity both in basic and in PMA/Io-induced conditions. We further found that SIRT1 was involved in transcription complex binding on the ICAM-1 promoter by chromatin immunoprecipitation (ChIP) assays. Furthermore, SIRT1 RNAi increased NF-κB p65 binding ability to the ICAM-1 promoter by ChIP assays. Overall, these data suggests that SIRT1 inhibits ICAM-1 expression in endothelial cells, which may contribute to its anti-atherosclerosis effect.