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KMID : 0043320150380010081
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Archives of Pharmacal Research
2015 Volume.38 No. 1 p.81 ~ p.97
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Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [Ca2+]i mobilization and fibrinogen binding via phosphorylation of IP3R and VASP
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Lee Dong-Ha
Kwon Hyuk-Woo
Kim Hyun-Hong
Lim Deok-Hwi
Nam Gi-Suk
Shin Jung-Hae
Kim Yun-Yi
Kim Jong-Lae
Lee Jong-Jin
Kwon Ho-Kyun
Park Hwa-Jin
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Abstract
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In this study, we investigated the effect of cordycepin-enriched (CE)-WIB801C from Cordyceps militaris on ADP (20 μM)-stimulated platelet aggregation. CE-WIB801C dose-dependently inhibited ADP-induced platelet aggregation, and its IC50 value was 18.5 μg/mL. CE-WIB801C decreased TXA2 production, but did not inhibit the activities of COX-1 and thromboxane synthase (TXAS) in ADP-activated platelets, which suggests that the inhibition of TXA2 production by CE-WIB801C is not resulted 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-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased CE-WIB801C-inhibited [Ca2+]i mobilization, and strongly inhibited CE-WIB801C-increased IP3RI (Ser1756) phosphorylation. CE-WIB801C elevated the phosphorylation of VASP (Ser157), an A-kinase substrate, but inhibited fibrinogen binding to αIIb/β3. These results suggest that CE-WIB801C-elevated cAMP involved in IP3RI (Ser1756) phosphorylation to inhibit [Ca2+]i mobilization and, VASP (Ser157) phosphorylation to inhibit αIIb/β3 activation. Therefore, in this study, we demonstrate that CE-WIB801C may have a preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.
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KEYWORD
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CE-WIB801C, Ca2+, Cordycepin, Antiplatelet activity, IP3RI (Ser1756), VASP (Ser157)
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