Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [Ca(2+)] i mobilization and fibrinogen binding via phosphorylation of IP 3R and VASP.
Arch Pharm Res
; 38(1): 81-97, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25001901
ABSTRACT
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 [Ca(2+)]i mobilization, and increased cAMP level and IP3RI (Ser(1756)) phosphorylation in ADP-activated platelets. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased CE-WIB801C-inhibited [Ca(2+)]i mobilization, and strongly inhibited CE-WIB801C-increased IP3RI (Ser(1756)) phosphorylation. CE-WIB801C elevated the phosphorylation of VASP (Ser(157)), an A-kinase substrate, but inhibited fibrinogen binding to αIIb/ß3. These results suggest that CE-WIB801C-elevated cAMP involved in IP3RI (Ser(1756)) phosphorylation to inhibit [Ca(2+)]i mobilization and, VASP (Ser(157)) phosphorylation to inhibit αIIb/ß3 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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Base de dados:
MEDLINE
Assunto principal:
Fosfoproteínas
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Fibrinogênio
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Extratos Vegetais
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Moléculas de Adesão Celular
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Difosfato de Adenosina
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Desoxiadenosinas
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Sinalização do Cálcio
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Receptores de Inositol 1,4,5-Trifosfato
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Proteínas dos Microfilamentos
Idioma:
En
Revista:
Arch Pharm Res
Ano de publicação:
2015
Tipo de documento:
Article