Cordycepin-Enriched WIB801C from Cordyceps militaris Inhibits Collagen-Induced Ca2+i Mobilization via cAMP-Dependent Phosphorylation of Inositol 1, 4, 5-Trisphosphate Receptor in Human Platelets.
- Author:
Dong Ha LEE
1
;
Hyun Hong KIM
;
Hyun Jeong CHO
;
Young Bin YU
;
Hyo Chan KANG
;
Jong Lae KIM
;
Jong Jin LEE
;
Hwa Jin PARK
Author Information
1. Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, Gimhae 621-749, Republic of Korea. mlsjpark@inje.ac.kr
- Publication Type:Original Article
- Keywords:
CE-WIB801C;
cAMP;
TXA2;
Ca2+;
IP3R
- MeSH:
1-Butanol;
Atherosclerosis;
Blood Platelets;
Cordyceps*;
Cyclic AMP-Dependent Protein Kinases;
Cyclooxygenase 1;
Humans;
Inhibitory Concentration 50;
Inositol*;
Myocardial Infarction;
Phosphorylation*;
Platelet Aggregation;
Thrombosis;
Thromboxane A2
- From:Biomolecules & Therapeutics
2014;22(3):223-231
- CountryRepublic of Korea
- Language:English
-
Abstract:
In this study, we prepared cordycepin-enriched (CE)-WIB801C, a n-butanol extract of Cordyceps militaris-hypha, and investigated the effect of CE-WIB801C on collagen-induced human platelet aggregation. CE-WIB801C dose-dependently inhibited collagen-induced platelet aggregation, and its IC50 value was 175 microg/ml. CE-WIB801C increased cAMP level more than cGMP level, but inhibited collagen-elevated [Ca2+]i mobilization and thromboxane A2 (TXA2) production. cAMP-dependent protein kinase (A-kinase) inhibitor Rp-8-Br-cAMPS increased the CE-WIB801C-downregulated [Ca2+]i level in a dose dependent manner, and strongly inhibited CE-WIB801C-induced inositol 1, 4, 5-trisphosphate receptor (IP3R) phosphorylation. These results suggest that the inhibition of [Ca2+]i mobilization by CE-WIB801C is resulted from the cAMP/A-kinase-dependent phosphorylation of IP3R. CE-WIB801C suppressed TXA2 production, but did not inhibit the activities of cyclooxygenase-1 (COX-1) and TXA2 synthase (TXAS). These results suggest that the inhibition of TXA2 production by WIB801C is not resulted from the direct inhibition of COX-1 and TXAS. In this study, we demonstrate that CE-WIB801C with cAMP-dependent Ca2+-antagonistic antiplatelet effects may have preventive or therapeutic potential for platelet aggregation-mediated diseases, such as thrombosis, myocardial infarction, atherosclerosis, and ischemic cerebrovascular disease.
