Abstract
Caffeic acid (CA) is a well-known to inhibit thrombogenic thromboxane A2 (TXA2) production, but there are no reports for the supply and usage of its precursor arachidonic acid (AA) and the release of serotonin, another thrombogenic molecule. In this study, we investigated the effect of CA on the phosphorylation of AA supply enzymes [cytosolic phospholipase A2α (cPLA2α), and phospholipase Cγ2 (PLCγ2)] and AA utilization enzymes [cyclooxygenase (COX)-1, TXA2 synthase (TXAS)] in collagen-activated human platelets. p38 MAPK phosphorylation associated with TXA2 production and c-Jun NH2-terminal kinase 1 (JNK1) phosphorylation associated with serotonin release were also determined. CA inhibited collagen-induced TXA2 production in a dose-dependent manner. It acted by counteracting the phosphorylation of AA release enzyme (PLCγ2) and AA utilization enzymes (COX-1 and TXAS) without affecting p38 MAPK and cPLA2α in collagenactivated human platelets. CA decreased collagen-released serotonin by inhibiting JNK1 phosphorylation. Therefore, our data demonstrate that CA might protect TXA2- and serotonin-mediated thrombogenesis.
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