Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4).
Resveratrol, an important antioxidant found in grapes and wine, is likely to contribute to red wine's potential to prevent human cardiovascular disease. In addition to its known (direct) antioxidant effect, we have found that resveratrol also regulates the gene expression of pro-oxidative and anti-oxidative enzymes in human endothelial cells. NADPH oxidases (Nox) are the predominant producers of superoxide in the vasculature, whereas superoxide dismutase (SOD) and glutathione peroxidase 1 (GPx1) are the major enzymes responsible for the inactivation of superoxide and hydrogen peroxide, respectively. Incubation of human umbilical vein endothelial cells (HUVEC) and HUVEC-derived EA.hy 926 cells with resveratrol resulted in a concentration- and time-dependent downregulation of Nox4, the most abundant NADPH oxidase catalytic subunit (quantitative real-time RT-PCR). The same resveratrol regimen upregulated the mRNA expression of SOD1 and GPx1. The addition the protein levels of SOD1 and GPx1 were enhanced by resveratrol in a concentration-dependent manner (Western blot analyses). Pretreatment of EA.hy 926 cells with resveratrol completely abolished DMNQ-induced oxidative stress. Thus, the expressional suppression of pro-oxidative genes (such as NADPH oxidase) and induction of anti-oxidative enzymes (such as SOD1 and GPx1) might be an important component of the vascular protective effect of resveratrol.
Spanier
G
G
Department of Pharmacology, Johannes Gutenberg University, Mainz, Germany.
Xu
H
H
Xia
N
N
Tobias
S
S
Deng
S
S
Wojnowski
L
L
Forstermann
U
U
Li
H
H
D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005979:Glutathione Peroxidase / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000096:biosynthesis* / Q000235:genetics; D009285:Naphthoquinones / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D017382:Reactive Oxygen Species; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics; D000072105:Superoxide Dismutase-1; D000094765:Glutathione Peroxidase GPX1
D000975:Antioxidants; D009285:Naphthoquinones; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; C000606290:SOD1 protein, human; D013267:Stilbenes; C063002:2,3-dimethoxy-1,4-naphthoquinone; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human; D000077185:Resveratrol; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human