Inhibitory effect of resveratrol derivative BTM-0512 on high glucose-induced cell senescence involves dimethylaminohydrolase/asymmetric dimethylarginine pathway

Summary 1. It has been reported that resveratrol exerts the inhibitory effects on aging through activation of sirtuin 1 (SIRT1) and dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway involved in the high glucose‐induced endothelial cell senescence. 2. The aims...

Full description

Saved in:
Bibliographic Details
Published in:Clinical and experimental pharmacology & physiology 2010-05, Vol.37 (5-6), p.630-635
Main Authors: Yuan, Qiong, Peng, Jun, Liu, Si-Yu, Wang, Chen-Jing, Xiang, Da-Xiong, Xiong, Xiao-Ming, Hu, Chang-Ping, Li, Yuan-Jian
Format: Article
Language:English
Subjects:
Amidohydrolases - genetics
Amidohydrolases - metabolism
Antioxidants - pharmacology
Arginine - analogs & derivatives
Arginine - metabolism
BTM-0512
Cell Culture Techniques
Cell Line
Cellular Senescence - drug effects
dimethylarginine dimethylaminohydrolase
Dose-Response Relationship, Drug
Endothelial Cells - drug effects
Endothelial Cells - enzymology
Endothelial Cells - metabolism
Endothelium, Vascular - drug effects
Endothelium, Vascular - enzymology
Endothelium, Vascular - metabolism
Gene Expression - drug effects
Glucose - adverse effects
Humans
hyperglycaemia
Nitric Oxide - biosynthesis
Nitric Oxide Synthase - metabolism
Reactive Oxygen Species - metabolism
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
senescence
sirtuin 1
Sirtuin 1 - metabolism
Stilbenes - analysis
Stilbenes - pharmacology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary 1. It has been reported that resveratrol exerts the inhibitory effects on aging through activation of sirtuin 1 (SIRT1) and dimethylarginine dimethylaminohydrolase (DDAH)/asymmetric dimethylarginine (ADMA) pathway involved in the high glucose‐induced endothelial cell senescence. 2. The aims of this work were to explore whether BTM‐0512, a novel derivative of resveratrol, was able to exert the beneficial effect on high glucose‐induced cellular senescence through regulating the DDAH/ADMA pathway and to explore whether the regulatory effect of BTM‐0512 on DDAH/ADMA pathway was related to the activation of SIRT1. 3. The senescence model of endothelial cells was induced by high glucose and the cells were collected for the determination of β‐galactosidase and DDAH activity, ADMA level, DDAH and SIRT1 mRNA expression. 4. The results showed that high glucose significantly increased the ratio of senescent cells concomitantly with the decreased DDAH activity, the downregulated DDAH2 and SIRT1 mRNA expressions and the increased ADMA levels, which were attenuated by pretreatment with BTM‐0512. 5. The beneficial effects of BTM‐0512 on high glucose‐induced senescence were blocked by splimtomicin, the specific inhibitor of SIRT1, or by silencing DDAH2 expression. 6. The results suggest that BTM‐0512 was able to exert the beneficial effects on high glucose‐induced cellular senescence through regulating the DDAH/ADMA pathway, and its regulatory effect on DDAH/ADMA pathway was related to the activation of SIRT1.
ISSN:0305-1870
1440-1681
DOI:10.1111/j.1440-1681.2010.05368.x