Inhibitory effect of resveratrol derivative BTM-0512 on high glucose-induced cell senescence involves dimethylaminohydrolase/asymmetric dimethylarginine pathway.
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 beta-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.
Department of Pharmacology, School of Pharmaceutical Science, Central South University, Changsha 410078, China.
Qiong
Q
Yuan
Jun
J
Peng
Si-Yu
SY
Liu
Chen-Jing
CJ
Wang
Da-Xiong
DX
Xiang
Xiao-Ming
XM
Xiong
Chang-Ping
CP
Hu
Yuan-Jian
YJ
Li
D000581:Amidohydrolases / Q000235:genetics / Q000378:metabolism*; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism; D018929:Cell Culture Techniques; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000009:adverse effects*; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D056564:Sirtuin 1 / Q000378:metabolism; D013267:Stilbenes / Q000032:analysis* / Q000494:pharmacology*
C497286:3,4',5-trimethoxystilbene; D000975:Antioxidants; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013267:Stilbenes; C487735:dimethylarginine; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000581:Amidohydrolases; C447939:SIRT1 protein, human; D056564:Sirtuin 1; C059999:dimethylargininase; D005947:Glucose; D000077185:Resveratrol