Effect of aspirin on high glucose-induced senescence of endothelial cells

IMR OpenIR

	Effect of aspirin on high glucose-induced senescence of endothelial cells
其他题名	Effect of aspirin on high glucose-induced senescence of endothelial cells
	Yi Tongning 1; Zhao Hongyu 1; Zhang Jingsheng 2; Shan Haiyan 1; Meng Xin 1; Zhang Jin 1
	2009
发表期刊	CHINESE MEDICAL JOURNAL
ISSN	0366-6999
卷号	122 期号:24 页码:3055-3061
摘要	Background Endothelial cell senescence is accelerated under high glucose condition, which may contribute to the vascular complications in the diabetics. It has been proved that aspirin has multiple cytoprotective effects. This study aimed to investigate the effect of aspirin on high glucose-induced endothelial cell senescence and its possible mechanism.
其他摘要	Background Endothelial cell senescence is accelerated under high glucose condition, which may contribute to the vascular complications in the diabetics. It has been proved that aspirin has multiple cytoprotective effects. This study aimed to investigate the effect of aspirin on high glucose-induced endothelial cell senescence and its possible mechanism.Methods Human umbilical venous endothelial cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with different treatments including the normal glucose (5.5 mmol/L), high glucose (33 mmol/L) and aspirin (0.01-1.00 mmol/L) with high glucose. And 300 μmol/L L-NAME was added to the culture medium when needed. After 48 hours, SA-p-gal staining was used to evaluate the senescence. Total nitric oxide (NO) production and NO synthase (NOS) activity were measured using Griess reaction and molecular probes of 3-amino-4-aminomethyl-2', 7'- difluorescein, diacetate. The level of intracellular reactive oxygen species was monitored by flow cytometry using 2', 7'-dichlorofluorescein diacetate. Endothelial NOS (eNOS), caveolin-1 protein expressions and caveolin-1/eNOS interaction were analyzed by immunoblotting and immunoprecipitation respectively. Asymmetric dimethylarginine (ADMA) concentration was determined by high-performance liquid chromatography.Results Exposure to 33 mmol/L glucose for 48 hours significantly increased the number of SA-p-gal positive cells. Co-incubation with aspirin markedly inhibited SA-p-gal activity dose-dependently. Aspirin increased NOS activity with eNOS protein expression unchanged and increased NO levels and alleviated oxidative stress. Consistent with these findings, caveolin-1 expression, caveolin-1/eNOS interaction and ADMA accumulation were also decreased. All the inhibitory effects of aspirin on senescence were completely obliterated by L-NAME, the NOS inhibitor. Conclusion The anti-senescent effects of aspirin are fulfilled by increasing NO production via the up-regulation of NOS activity and preventing caveolin-1 expression, caveolin-1/eNOS interaction and ADMA accumulation.
关键词	NITRIC-OXIDE SYNTHASE OXIDATIVE STRESS ASYMMETRIC DIMETHYLARGININE HUMAN ATHEROSCLEROSIS CELLULAR SENESCENCE L-ARGININE CAVEOLIN-1 ACTIVATION MECHANISM PATHWAY aspirin high glucose senescence nitric oxide caveolin-1 asymmetric dimethylarginine
收录类别	CSCD
语种	英语
资助项目	[People's Government of Shenyang City]
CSCD记录号	CSCD:3775636
引用统计
文献类型	期刊论文
条目标识符	http://ir.imr.ac.cn/handle/321006/157936
专题	中国科学院金属研究所
作者单位	1.中国科学院金属研究所 2.辽宁大学
推荐引用方式 GB/T 7714	Yi Tongning,Zhao Hongyu,Zhang Jingsheng,et al. Effect of aspirin on high glucose-induced senescence of endothelial cells[J]. CHINESE MEDICAL JOURNAL,2009,122(24):3055-3061.
APA	Yi Tongning,Zhao Hongyu,Zhang Jingsheng,Shan Haiyan,Meng Xin,&Zhang Jin.(2009).Effect of aspirin on high glucose-induced senescence of endothelial cells.CHINESE MEDICAL JOURNAL,122(24),3055-3061.
MLA	Yi Tongning,et al."Effect of aspirin on high glucose-induced senescence of endothelial cells".CHINESE MEDICAL JOURNAL 122.24(2009):3055-3061.