Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists.
Epigallocatechin-3-gallate (EGCG), a component of green tea, inhibits human platelet aggregation and cytosolic [Ca(2+)](c) increases more strongly when these processes are induced by thrombin than by the non-proteolytic thrombin receptor activating peptide (TRAP), thromboxane mimetic U46619, or fluoroaluminate. In line with the previously demonstrated EGCG anti-proteolytic activity, a marked inhibition on aggregation is obtained by pre-incubation of thrombin with EGCG prior to addition to cellular suspension. The catechin also reduces cellular Ca(2+) influx following thapsigargin-induced calcium emptying of endoplasmic reticulum, and the agonist-promoted cellular protein tyrosine phosphorylation. Both tyrosine kinases Syk and Lyn, immuno-precipitated from stimulated platelets, are greatly inhibited upon cellular pre-incubation with EGCG, which also inhibits the in vitro auto-phosphorylation and exogenous activity of these two enzymes purified from rat spleen. Both thrombin-induced aggregation and [Ca(2+)](c) increase are reduced in platelets from rats that drank green tea solutions. It is concluded that EGCG inhibits platelet activation, by hindering the thrombin proteolytic activity, and by reducing the agonist-induced [Ca(2+)](c) increase through inhibition of Syk and Lyn activities.
Department of Biological Chemistry and Institute of the Neuroscience of the Italian National Research Council (CNR), University of Padova, Italy.
Renzo
R
Deana
Loris
L
Turetta
Arianna
A
Donella-Deana
Massimo
M
Donà
Anna Maria
AM
Brunati
Lucia
L
De Michiel
Spiridione
S
Garbisa
D000818:Animals; D001792:Blood Platelets / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004792:Enzyme Precursors / Q000037:antagonists & inhibitors; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D010447:Peptide Hydrolases / Q000378:metabolism*; D015539:Platelet Activation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D000072377:Syk Kinase; D013662:Tea / Q000737:chemistry; D013917:Thrombin / Q000037:antagonists & inhibitors / Q000502:physiology; D019061:src-Family Kinases / Q000037:antagonists & inhibitors
D004792:Enzyme Precursors; D047908:Intracellular Signaling Peptides and Proteins; D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase; C000606898:Syk protein, rat; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D010447:Peptide Hydrolases; D013917:Thrombin; D002118:Calcium