title: Effect of resveratrol derivative BTM-0512 on high glucose-induced dysfunction of endothelial cells: role of SIRT1.
abstract: Hyperglycemia impairs the function of endothelial cells. Sirtuin 1 (SIRT1) is involved in regulating the function of endothelial cells. Resveratrol, a polyphenol found in many plant species, exerts protective effects on endothelial cells through activation of SIRT1. The aims of this work were to explore whether BTM-0512, a novel derivative of resveratrol, is able to exert beneficial effects on high glucose-induced dysfunction of endothelial cells through regulation of SIRT1. We found that high glucose significantly impaired the function of endothelial cells as shown by reduced tube formation, cell migration, and cell adhesion concomitantly with downregulation of mRNA expression of SIRT1 and vascular endothelial growth factor as well as increased tumor necrosis factor-α release and reactive oxygen species production. These effects of high glucose were inhibited by pretreatment with BTM-0512. The beneficial effects of BTM-0512 on high glucose-induced cell dysfunction were abolished by splitomicin, a specific inhibitor of SIRT1. The regulatory effects of BTM-0512 on high glucose-induced changes in vascular endothelial growth factor mRNA expression and tumor necrosis factor-α release were also abolished by splitomicin. The results suggest that BTM-0512 exerts beneficial effects on high glucose-induced endothelial cell dysfunction through regulation of the SIRT1 - reactive oxygen species - vascular endothelial growth factor - tumor necrosis factor-α pathway.
authors: Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha 410078, P.R. China.
authors: Qiong
authors: Q
authors: Yuan
authors: Lei
authors: L
authors: Chen
authors: Da-Xiong
authors: DX
authors: Xiang
authors: Yuan-Jian
authors: YJ
authors: Li
authors: Chang-Ping
authors: CP
authors: Hu
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D005947:Glucose / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D056564:Sirtuin 1 / Q000096:biosynthesis / Q000502:physiology*; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
chemical_list: C497286:3,4',5-trimethoxystilbene; D000975:Antioxidants; D017382:Reactive Oxygen Species; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D005947:Glucose; D000077185:Resveratrol