Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [Ca2+]i mobilization and fibrinogen binding via phosphorylation of IP3R and VASP

다국어 초록 (Multilingual Abstract)

In this study, we investigated the effect ofcordycepin-enriched (CE)-WIB801C from Cordyceps militarison ADP (20 lM)-stimulated platelet aggregation. CE-WIB801C dose-dependently inhibited ADP-inducedplatelet aggregation, and its IC50 value was 18.5 lg/mL. CE-WIB801C decreased TXA2 production, but did notinhibit the activities of COX-1 and thromboxane synthase(TXAS) in ADP-activated platelets, which suggests that theinhibition of TXA2 production by CE-WIB801C is notresulted from the direct inhibition of COX-1 and TXAS.
CE-WIB801C inhibited ATP release and [Ca2＋]i mobilization,and increased cAMP level and IP3RI (Ser1756)phosphorylation in ADP-activated platelets. cAMP-dependentprotein kinase (A-kinase) inhibitor Rp-8-Br-cAMPSincreased CE-WIB801C-inhibited [Ca2＋]i mobilization,and strongly inhibited CE-WIB801C-increased IP3RI(Ser1756) phosphorylation. CE-WIB801C elevated thephosphorylation of VASP (Ser157), an A-kinase substrate,but inhibited fibrinogen binding to aIIb/b3. These resultssuggest that CE-WIB801C-elevated cAMP involved inIP3RI (Ser1756) phosphorylation to inhibit [Ca2＋]i mobilizationand, VASP (Ser157) phosphorylation to inhibit aIIb/b3 activation. Therefore, in this study, we demonstrate thatCE-WIB801C may have a preventive or therapeuticpotential for platelet aggregation-mediated diseases, suchas thrombosis, myocardial infarction, atherosclerosis, andischemic cerebrovascular disease.

참고문헌 (Reference)

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