title: Inhibitory effects of resveratrol on platelet activation induced by thromboxane a(2) receptor agonist in human platelets.
abstract: Resveratrol (RSVL), a polyphenolic compound found in red wine is believed to be a contributor in decreasing the incidence of coronary heart disease. Although its primary target is unknown, it blocks platelet aggregation by an ill-defined mechanism. Protein kinase C (PKC), which would redistribute from the cytosol to the platelet membrane upon platelet stimulation, plays a key role in the signal transduction system of platelets in human. In this study, we investigated the effect of RSVL and a PKC inhibitor (DL-erythro-1,3-Dihydroxy-2-aminooctadecane, PKCI) on platelet aggregation induced by a thromboxane A(2) receptor agonist (U46619, 9,11-Dideoxy-11α, 9α-epoxymethanoprostaglandin F(2α)) using a platelet aggregometer. We also studied the platelet membranebound fibrinogen (PFig) content and the activity of protein kinase C (PKC) in platelets from healthy volunteers using flow cytometry, and a phosphorimaging system, respectively. Our results showed that RSVL blocked platelet aggregation and PFig content induced by U46619 in a concentration-dependent manner. PKCI and RSVL had an additive effect in inhibiting platelet aggregation and PFig content. Furthermore, RSVL (final concentration 50 μM) remarkably depressed the activity of PKC in the membrane of platelets and the percentage of membrane PKC activity in total PKC activity. Taken together, these results suggested that RSVL suppressed U46619-induced platelet aggregation and PFig content partially through the inhibition of the activity of PKC in platelets.
authors.affiliation: Department of Cardiovascular Disease, Traditional Chinese-Mongolian Hospital of Inner Mongolia Autonomous Region, Hohhot 010020, P. R. China. yangyumin331@126.com
authors.forename: Yumin
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Huiping
authors.initials: H
authors.lastname: An
authors.forename: Zhigao
authors.initials: Z
authors.lastname: Zao
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D010936:Plant Extracts / Q000494:pharmacology*; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000097:blood; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D027843:Vitis / Q000737:chemistry*; D055815:Young Adult
chemical_list: D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013267:Stilbenes; D014662:Vasoconstrictor Agents; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D005340:Fibrinogen; D011493:Protein Kinase C; D000077185:Resveratrol