title: Resveratrol protects vascular smooth muscle cells against high glucose-induced oxidative stress and cell proliferation in vitro.
abstract: BACKGROUND
  Resveratrol exhibits beneficial effects against numerous degenerative diseases at different stages of pathogenesis. This study investigated potential mechanisms and resveratrol effects on high glucose (HG)-induced oxidative stress (30 mM D-glucose, 30 min) and cell proliferation (30 mM D-glucose, 24 h) in vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  Intracellular reactive oxygen species (ROS) generation was detected by 2',7'-dichlorofluorescein diacetate (DCFH-DA). Total antioxidant capacity (TAC), malonyldialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) were measured to evaluate oxidative stress. VSMC proliferation was measured by CCK-8 assays and through propidium iodide-based cell cycle analysis. Expression of NAD(P)H oxidase, proliferation proteins, and cell signalling were assessed by immunoblot analysis.
  
  
  RESULTS
  Co-treatment of primary cultures of VSMCs with 1-100 μM resveratrol decreased HG-induced ROS overproduction (P<0.05). Resveratrol also abolished HG-induced phosphorylation of oxidase subunit p47 phox and reduced HG-induced cyclin D1, cyclin E, and PCNA expression in a concentration-dependent manner. Furthermore, resveratrol (10 μM) attenuated HG-induced phosphorylation of Akt, p38 mitogen-activated protein kinase (MAPK), ERK 1/2, and JNK1/2 without affecting total levels. HG stimulation enhanced downstream IκB-α phosphorylation and NF-κB activity, and resveratrol repressed these effects.
  
  
  CONCLUSIONS
  Resveratrol inhibits HG-induced oxidative stress and VSMC proliferation by suppressing ROS generation, NADPH oxidase, Akt phosphorylation, p38 MAPK/JNK/ERK phosphorylation, and IκB-α and NF-κB activities.
authors: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).
authors: Rong
authors: R
authors: Guo
authors: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).
authors: Weiming
authors: W
authors: Li
authors: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).
authors: Baoxin
authors: B
authors: Liu
authors: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).
authors: Shuang
authors: S
authors: Li
authors: Department of Cardiology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, China (mainland).
authors: Buchun
authors: B
authors: Zhang
authors: Department of Cardiology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China (mainland).
authors: Yawei
authors: Y
authors: Xu
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000633:toxicity*; D020672:I-kappa B Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D019255:NADPH Oxidases / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D020011:Protective Agents / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D015415:Biomarkers; D020672:I-kappa B Proteins; C000606206:Nfkbia protein, rat; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013267:Stilbenes; D000072000:NF-KappaB Inhibitor alpha; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D000077185:Resveratrol