Differential effect of resveratrol on nitric oxide production in endothelial f-2 cells.
We examined the rapid effect of resveratrol on nitric oxide (NO) production in endothelial F-2 cells. During an incubation period of 10 min, resveratrol at low concentrations (<20 microM) had no effect on NO production, whereas it significantly increased NO production at high concentrations (>50 microM). In contrast, pretreatment with resveratrol at low concentrations caused a significant decrease in vascular endothelial growth factor (VEGF)-stimulated NO production. Resveratrol failed to induce phosphorylation of endothelial NO synthase (eNOS) and VEGF receptor and did not affect autophosphorylation of the VEGF receptor. However, resveratrol markedly suppressed VEGF-induced eNOS phosphorylation. Resveratrol at high concentrations reduced the viability of F-2 cells as determined by 3-(4,5-dimethyl-2-thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) and dye exclusion methods. Resveratrol-stimulated NO production was completely abolished by the depletion of extracellular Ca2+. These results indicate that resveratrol stimulates NO production by a Ca(2+)-dependent mechanism and reduces VEGF-stimulated NO production by impairing a Ca(2+)-independent mechanism in endothelial F-2 cells. However, the stimulatory effect of resveratrol may be partly attributed to its cytotoxicity.
Takahashi
Satoru
S
First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, Yoshino, Nobeoka, Miyazaki 882-0072, Japan. satorutaka@phoenix.ac.jp
Uchiyama
Tomomi
T
Toda
Ken-Ichi
K
D000818:Animals; D015153:Blotting, Western; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D040262:Receptors, Vascular Endothelial Growth Factor / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*
D013267:Stilbenes; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D040262:Receptors, Vascular Endothelial Growth Factor; D000077185:Resveratrol