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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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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 [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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Acknowledgments

This study was supported by a Grant (NRF-2011-0012143 to Hwa-Jin Park) from Basic Science Research Program via the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology, Korea.

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The authors declare no conflict of interest.

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  1. Dong-Ha Lee

    Present address: Department of Biomedical Laboratory Science, Korea Nazarene University, 48, Wolbong-ro, Seobuk-gu, Cheonan, Chungnam, 331-778, Republic of Korea

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  1. Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, Inje University, 197, Inje-ro, Gimhae, Gyungnam, 621-749, Republic of Korea

    Dong-Ha Lee, Hyuk-Woo Kwon, Hyun-Hong Kim, Deok Hwi Lim, Gi Suk Nam, Jung-Hae Shin, Yun-Yi Kim & Hwa-Jin Park

  2. Bioscience and Biotechnology Team, Central Research Center, Whanin Pharm. Co., Ltd., 107, Gwanggyo-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 443-766, Republic of Korea

    Jong-Lae Kim, Jong-Jin Lee & Ho-Kyun Kwon

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Dong-Ha Lee, Hyuk-Woo Kwon, and Hyun-Hong Kim have contributed equally to this work.

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Lee, DH., Kwon, HW., Kim, HH. et al. Cordycepin-enriched WIB801C from Cordyceps militaris inhibits ADP-induced [Ca2+]i mobilization and fibrinogen binding via phosphorylation of IP3R and VASP. Arch. Pharm. Res. 38, 81–97 (2015). https://doi.org/10.1007/s12272-014-0436-z

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