Differential Effect of Resveratrol on Nitric Oxide Production in Endothelial F-2 Cells
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概要
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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 μM) had no effect on NO production, whereas it significantly increased NO production at high concentrations (>50 μM). 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 Ca2+-dependent mechanism and reduces VEGF-stimulated NO production by impairing a Ca2+-independent mechanism in endothelial F-2 cells. However, the stimulatory effect of resveratrol may be partly attributed to its cytotoxicity.
著者
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TAKAHASHI Satoru
First Department of Pathology, Nagoya City University Medical School
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Uchiyama Tomomi
First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and
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Toda Ken-ichi
Department of Dermatology, Kitano Hospital, Tazuke Kofukai Medical Research Institute
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Toda Ken-ichi
Department Of Dermatology Faculty Of Medicine Kyoto University
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Takahashi Satoru
First Department Of Biochemistry School Of Pharmaceutical Sciences Kyushu University Of Health And W
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Uchiyama Tomomi
First Department of Biochemistry, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare
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