Resveratrol inhibits polyphosphoinositide metabolism in activated platelets

摘要

The effects of resveratrol (trans-3,4,5-trihydroxystilbene) on activation responses and the polyphosphomositide metabolism in human blood platelets have been studied. Resveratrol partially inhibited secretory responses (liberation of dense granule nucleotides and lysosomal acid hydrolases), microparticle formation and protein phosphorylations induced by thrombin. The effects of resveratrol on phosphomositide metabolites, phosphatidate (PtdOH), phosphatidylinositol, (PtdIns), phosphatidylinositol-4-phosphate (PtdIns-4(5)-P), phosphatidylinositol 4,5-bisphosphate (PtdIns-4,5-P-2), phosphatidylinositol-3,4-bisphosphate (PtdIns-3,4-P-2) and phosphatidylinositol-3,4,5-trisphosphate (Ptdlns-3,4,5-P-3) were monitored in blood platelets prelabelled with [P-32]P-i. Resveratrol not only inhibited the marked increase in levels of PtdOH in platelets activated by thrombin (0.1 U/ml) but it decreased the steady state levels of the other polyphosphoinositide metabolites. The distribution of P-32 in phosphomositides in activated platelets was consistent with inhibition of CDP-DAG inositol transferase and a weak inhibition of Ptdlns-4(5)-P kinase. These observations show that resveratrol has a profound effect on phospholipids, particularly on polyphosphoinositide metabolism, and may decrease the amount of Ptdlns-4,5-P2 available for signalling in these cells. (c) 2005 Elsevier B.V All rights reserved.