RESUMO
The C-terminal peptide of thrombospondin (4N1-1) stimulates distinct signalling pathways but induces an activation-independent platelet aggregation. This study demonstrates inhibitory effects of epigallocatechin gallate (EGCG), a major flavonoid component of green tea, on 4N1-1-induced aggregation of washed human platelets. Thrombin (0.1 U/ml)-induced platelet aggregation was completely inhibited by prostaglandin E1 (PGE1, 300 nM). In contrast, platelet aggregation induced by 4N1-1 (100 microM) was not affected by PGE1. However, epigallocatechin gallate (EGCG), but not other catechins from green tea, concentration-dependently inhibited 4N1-1-induced platelet aggregation. Thus, dietary components, such as EGCG, may inhibit platelet function even under conditions, when 'classical' platelet inhibitors, such as cAMP-elevating agents, are not effective.
Assuntos
Alprostadil/farmacologia , Catequina/análogos & derivados , Catequina/farmacologia , Peptídeos/farmacologia , Inibidores da Agregação Plaquetária/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores de Proteases/farmacologia , Trombospondina 1/farmacologia , Células Cultivadas , Humanos , Testes de Função PlaquetáriaRESUMO
Epigallocatechin gallate (EGCG), a major component of green tea, has been previously shown to inhibit platelet aggregation. The effects of other green tea catechins on platelet function are not known. Pre-incubation with EGCG concentration-dependently inhibited thrombin-induced aggregation and phosphorylation of p38 mitogen-activated protein kinase and extracellular signal-regulated kinases-1/2. In contrast EGCG stimulated tyrosine phosphorylation of platelet proteins, including Syk and SLP-76 but inhibited phosphorylation of focal adhesion kinase. Other catechins did not inhibit platelet aggregation. Interestingly, when EGCG was added to stirred platelets, a tyrosine kinase-dependent stimulation of platelet aggregation was observed. The two other catechins containing a galloyl group in the 3' position (catechin gallate, epicatechin gallate) also stimulated platelet aggregation, while catechins without a galloyl group (catechin, epicatechin) or the catechin with a galloyl group in the 2' position (epigallocatechin) did not.
Assuntos
Plaquetas/efeitos dos fármacos , Catequina/análogos & derivados , Catequina/farmacologia , Chá/química , Citometria de Fluxo , Humanos , Fosforilação , Agregação Plaquetária/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Trombina/farmacologia , Tirosina/metabolismoRESUMO
A peptide from the C-terminal domain of thrombospondin-1 (4N1-1) has been proposed to stimulate platelet aggregation by a novel mechanism involving both an activation-independent agglutination and an activation-dependent, glycoprotein (GP) IIb/IIIa-mediated aggregation which involves GPVI signaling but does not involve CD47. The present study demonstrates that 4N1-1 stimulated a different pattern of signal transduction pathways than the GPVI agonist convulxin. Furthermore, 4N1-1-induced platelet aggregation was activation-independent and not dependent on GPVI or GPIIb/IIIa. Interestingly, 4N1-1 also stimulated activation-independent agglutination of different megakaryocytic and non-megakaryocytic cells. 4N1-1-induced cell agglutination but not platelet signaling was inhibited by anti-CD47 antibodies.