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Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway

Hubbard, G.P., Stevens, J.M., Cicmil, M., Sage, T., Jordan, P.A., Williams, C.M., Lovegrove, J.A. ORCID: https://orcid.org/0000-0001-7633-9455 and Gibbins, J.M. ORCID: https://orcid.org/0000-0002-0372-5352 (2003) Quercetin inhibits collagen-stimulated platelet activation through inhibition of multiple components of the glycoprotein VI signaling pathway. Journal of Thrombosis and Haemostasis, 1 (5). pp. 1079-1088. ISSN 1538-7933

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To link to this item DOI: 10.1046/j.1538-7836.2003.00212.x

Abstract/Summary

Background: The regulation of platelet function by pharmacological agents that modulate platelet signaling haspharmacolo proven a successful approach to the prevention of thrombosis. A variety of molecules present in the diet have been shown to inhibit platelet activation, including the antioxidant quercetin. Objectives: In this report we investigate the molecular mechanisms through which quercetin inhibits collagen-stimulated platelet aggregation. Methods: The effect of quercetin on platelet aggregation, intracellular calcium release, whole cell tyrosine phosphorylation and intracellular signaling events including tyrosine phosphorylation and kinase activity of proteins involved in the collagen-stimulated glycoprotein (GP) signaling pathway were investigated. Results: We report that quercetin inhibits collagen-stimulated whole cell protein tyrosine phosphorylation and intracellular mobilization of calcium, in a concentration-dependent manner. Quercetin was also found to inhibit various events in signaling generated by the collagen receptor GPVI. This includes collagen-stimulated tyrosine phosphorylation of the Fc receptor gamma-chain, Syk, LAT and phospholipase Cgamma2. Inhibition of phosphorylation of the Fc receptor gamma-chain suggests that quercetin inhibits early signaling events following stimulation of platelets with collagen. The activity of the kinases that phosphorylate the Fc receptor gamma-chain, Fyn and Lyn, as well as the tyrosine kinase Syk and phosphoinositide 3-kinase was also inhibited by quercetin in a concentration-dependent manner, both in whole cells and in isolation. Conclusions: The present results provide a molecular basis for the inhibition by quercetin of collagen-stimulated platelet activation, through inhibition of multiple components of the GPVI signaling pathway, and may begin to explain the proposed health benefits of high quercetin intake.

Item Type:Article
Refereed:Yes
Divisions:Life Sciences > School of Biological Sciences
Life Sciences > School of Chemistry, Food and Pharmacy > Department of Food and Nutritional Sciences
Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
ID Code:13307
Uncontrolled Keywords:collagen, GPVI, platelets, quercetin, RECEPTOR-GAMMA-CHAIN, TYROSINE PHOSPHORYLATION, AGGREGATION, FLAVONOIDS, INVOLVEMENT, CONVULXIN, MECHANISM, ADHESION, THROMBIN, CELLS
Publisher:Wiley-Blackwell

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