Resveratrol inhibits Ca2+ signals and aggregation of platelets
Mikio Marumo, Kazumi Ekawa, Ichiro Wakabayashi
Abstract
Abstract Background Resveratrol has been shown to inhibit platelet aggregation. However, the mechanism for this action of resveratrol remains to be clarified. The purpose of this study was to elucidate the Ca 2+ -related mechanism for the inhibitory action of resveratrol on platelet aggregation. Methods Ca 2+ entry and subsequent aggregation of human platelets induced by different stimulants including thrombin, thapsigargin, and 1-oleoyl-2-acetylglycerol (OAG) were measured by the fluorescence method and light transmittance method, respectively. Each stimulant was added to a nominally Ca 2+ -free medium containing platelets, and then CaCl 2 was added to the medium to induce Ca 2+ influx into platelets. Results Thapsigargin-induced Ca 2+ entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 6.25 μM or higher concentrations, while OAG-induced Ca 2+ entry and subsequent platelet aggregation were not affected by resveratrol at concentrations up to 50 μM. In the nominally Ca 2+ -free medium, thrombin induced a small transient increase in intracellular Ca 2+ concentrations, which was attenuated in the presence of resveratrol at 12.5 μM or higher concentrations. Thrombin-induced Ca 2+ entry into platelets and subsequent platelet aggregation were significantly inhibited in the presence of resveratrol at 12.5 μM or higher concentrations. Conclusions The results suggest that resveratrol inhibits thrombin-induced platelet aggregation through decreasing Ca 2+ release from its stores and inhibiting store-operated Ca 2+ influx into platelets.