Resveratrol attenuates thromboxane A2 receptor agonist-induced platelet activation by reducing phospholipase C activity.
Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring compound shown to decrease the incidence of thromboembolic disease. Although considerable data are available as to the inhibitory effect of resveratrol on the platelet aggregation and thrombopoiesis in human, its underlying mechanism, at the cellular level, has not been rigorously studied. In this experiment, we studied the effect of resveratrol and 1-[6-[[17-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione, a phospholipase C inhibitor (U-73122) on the thromboxane A2 receptor agonist (9,11-dideoxy-11 alpha,9 alpha-epoxymethanoprostaglandin F(2 alpha), U46619)-induced platelet aggregation, platelet P-selectin expression, and the activity of phospho-phospholipase C beta 3 (P-PLC beta 3) and total-phospholipase C beta 3 (T-PLC beta 3), which play key roles in the signal transduction system of platelet in human. It was found that resveratrol blocked platelet aggregation and platelet P-selectin expression induced by U46619 in a concentration-dependent manner. U-73122 and resveratrol had additive effect in inhibiting platelet aggregation and platelet P-selectin expression. Resveratrol (final concentration was 50 microM) could reduce the ratio of P-PLC beta 3 to T-PLC beta 3. Taken together, these results show that resveratrol suppresses U46619-induced platelet aggregation and P-selectin expression partly through the decrease of the activity of phospholipase C beta of platelets.
Yang
Yu-Min
YM
Department of Cardiovascular Disease, the First Affiliated Hospital, Medical School of ZheJiang University, HangZhou, China.
Chen
Jun-Zhu
JZ
Wang
Xing-Xiang
XX
Wang
Shi-Jun
SJ
Hu
Hu
H
Wang
Hong-Qiang
HQ
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015153:Blotting, Western; D002316:Cardiotonic Agents / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004963:Estrenes / Q000494:pharmacology; D005434:Flow Cytometry; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D019007:P-Selectin / Q000096:biosynthesis; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000494:pharmacology; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000819:agonists*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects; D013267:Stilbenes / Q000494:pharmacology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors*
D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D004963:Estrenes; D007527:Isoenzymes; D019007:P-Selectin; D010975:Platelet Aggregation Inhibitors; D011760:Pyrrolidinones; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013267:Stilbenes; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D010738:Type C Phospholipases; D000077185:Resveratrol