title: Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [Ca(2+)] i mobilization and fibrinogen binding via phosphorylation of IP 3R and VASP.
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/β3. 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/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.
authors.affiliation: Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197, Inje-ro, Gimhae, Gyungnam, 621-749, Republic of Korea.
authors.forename: Dong-Ha
authors.initials: DH
authors.lastname: Lee
authors.forename: Hyuk-Woo
authors.initials: HW
authors.lastname: Kwon
authors.forename: Hyun-Hong
authors.initials: HH
authors.lastname: Kim
authors.forename: Deok Hwi
authors.initials: DH
authors.lastname: Lim
authors.forename: Gi Suk
authors.initials: GS
authors.lastname: Nam
authors.forename: Jung-Hae
authors.initials: JH
authors.lastname: Shin
authors.forename: Yun-Yi
authors.initials: YY
authors.lastname: Kim
authors.forename: Jong-Lae
authors.initials: JL
authors.lastname: Kim
authors.forename: Jong-Jin
authors.initials: JJ
authors.lastname: Lee
authors.forename: Ho-Kyun
authors.initials: HK
authors.lastname: Kwon
authors.forename: Hwa-Jin
authors.initials: HJ
authors.lastname: Park
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D032661:Cordyceps / Q000737:chemistry; D000242:Cyclic AMP / Q000378:metabolism; D051545:Cyclooxygenase 1 / Q000378:metabolism; D003839:Deoxyadenosines / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism*; D041743:Herb-Drug Interactions; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000378:metabolism; D013930:Thromboxane-A Synthase / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: C105593:8-bromoadenosine-3',5'-cyclic monophosphorothioate; D015815:Cell Adhesion Molecules; D003839:Deoxyadenosines; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008840:Microfilament Proteins; D010750:Phosphoproteins; D010936:Plant Extracts; D010975:Platelet Aggregation Inhibitors; D013873:Thionucleotides; C000605556:WIB801C; D000098662:Vasodilator-Stimulated Phosphoprotein; D015124:8-Bromo Cyclic Adenosine Monophosphate; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D005340:Fibrinogen; D000242:Cyclic AMP; D051545:Cyclooxygenase 1; D013930:Thromboxane-A Synthase; C058120:cordycepin; D002118:Calcium