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

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WOS被引频次:33
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成果类型:
期刊论文
作者:
Yuan, Qiong;Peng, Jun;Liu, Si‐Yu;Wang, Chen‐Jing;Xiang, Da‐Xiong;Xiong, Xiao‐Ming;Hu, Chang‐Ping;Li, Yuan‐Jian
通讯作者:
Li, Yuan-Jian
作者机构:
[Liu, Si‐Yu; Hu, Chang‐Ping; Peng, Jun; Yuan, Qiong; Wang, Chen‐Jing; Li, Yuan‐Jian; Xiong, Xiao‐Ming] Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410078, Hunan, Peoples R China.
[Hu, Chang‐Ping; Peng, Jun; Li, Yuan‐Jian] Cent S Univ, Sch Pharmaceut Sci, Hunan Prov Key Lab Cardiovasc Res, Changsha 410078, Hunan, Peoples R China.
[Xiang, Da‐Xiong] Cent S Univ, Xiangya Hosp 2, Clin Pharm & Pharmacol Inst, Changsha 410078, Hunan, Peoples R China.
通讯机构:
[Li, Yuan-Jian] Cent S Univ, Sch Pharmaceut Sci, Dept Pharmacol, Changsha 410078, Hunan, Peoples R China.
语种:
英文
关键词:
BTM‐0512;dimethylarginine dimethylaminohydrolase;hyperglycaemia;senescence;sirtuin 1
期刊:
Clinical and Experimental Pharmacology and Physiology
ISSN:
1440-1681
年:
2010
卷:
37
期:
5-6
页码:
630-635
文献类别:
WOS:Article
所属学科:
ESI学科类别:药理学&毒理学;WOS学科类别:Pharmacology & Pharmacy;Physiology
入藏号:
基金类别:
National Basic Research Program of China [2007CB512007]; National Nature Science of China [30700319]; Central South University [07MX24]; Graduate degree thesis Innovation Foundation of Central South University [2008yb027, 2340-7433400000]
机构署名:
本校为第一且通讯机构
院系归属:
湘雅药学院
湘雅医院(第一临床学院)
湘雅二医院(第二临床学院)
摘要:
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.

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