Green tea epigallocatechin-3-gallate inhibits platelet signalling pathways triggered by both proteolytic and non-proteolytic agonists

被引:29
作者
Deana, R
Turetta, L
Donella-Deana, A [1 ]
Donà, M
Brunati, AM
De Michiel, L
Garbisa, S
机构
[1] Univ Padua, Dept Biol Chem, Padua, Italy
[2] Univ Padua, Inst Neurosci, Italian Natl Res Council, Padua, Italy
[3] Univ Padua, Dept Expt Biomed Sci, Padua, Italy
关键词
epigallocatechin-3-gal late (EGCG); thrombin proteolytic activity; platelet cytosolic Ca2+; non-receptor tyrosine kinases;
D O I
10.1055/s-0037-1613474
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Epigallocatechin-3-gallate (EGCG), a component of green tea, inhibits human platelet aggregation and cytosolic [Ca2+](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 Ca2+ 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 [Ca2+](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 [Ca2+](c) increase through inhibition of Syk and Lyn activities.
引用
收藏
页码:866 / 874
页数:9
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