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KMID : 0603820170230030251
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Journal of Experimental & Biomedical Science
2017 Volume.23 No. 3 p.251 ~ p.260
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Inhibitory Effects of Cordycepin on Platelet Activation via Regulation of Cyclic Adenosine Monophosphate-downstream Pathway
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Lee Dong-Ha
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Abstract
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Platelet activation is essential at the sites of vascular injury, which leads to hemostasis through adhesion, aggregation, and secretion process. However, potent and continuous platelet activation may be an important reason of circulatory disorders. Therefore, proper regulation of platelet activation may be an effective treatment for vascular diseases. In this
research, inhibitory effects of cordycepin (3'-deoxyadenosine) on platelet activation were determined. As the results,
cordycepin increased cAMP and cGMP, which are intracellular Ca2+-antagonists. In addition, cordycepin reduced collagenelevated [Ca2+]i mobilization, which was increased by a cAMP-dependent protein kinase (PKA) inhibitor (Rp-8-BrcAMPS), but not a cGMP-protein kinase (PKG) inhibitor (Rp-8-Br-cGMPS). Furthermore, cordycepin increased IP3RI
(Ser1756) phosphorylation, indicating inhibition of IP3-mediated Ca2+ release from internal store via the IP3RI, which was strongly inhibited by Rp-8-Br-cAMPS, but was not so much inhibited by Rp-8-Br-cGMPS. These results suggest that the
reduction of [Ca2+]i mobilization is caused by the cAMP/A-kinase-dependent IP3RI (Ser1756) phosphorylation. In addition,
cordycepin increased the phosphorylation of VASP (Ser157) known as PKA substrate, but not VASP (Ser239) known as
PKG substrate. Cordycepin-induced VASP (Ser157) phosphorylation was inhibited by Rp-8-Br-cAMPS, but was not
inhibited by Rp-8-Br-cGMPS, and cordycepin inhibited collagen-induced fibrinogen binding to αIIb/β3, which was increased by Rp-8-Br-cAMPS, but was not inhibited by Rp-8-Br-cGMPS. These results suggest that the inhibition of
αIIb/β3 activation is caused by the cAMP/A-kinase-dependent VASP (Ser157) phosphorylation. In conclusion, these
results demonstrate that inhibitory effects of cordycepin on platelet activation were due to inhibition of [Ca2+]i mobilization
through cAMP-dependent IP3RI (Ser1756) phosphorylation and suppression of αIIb/β3 activation through cAMP-dependent
VASP (Ser157) phosphorylation. These results strongly indicated that cordycepin might have therapeutic or preventive
potential for platelet activation-mediated disorders including thrombosis, atherosclerosis, myocardial infarction, or
cardiovascular disease.
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KEYWORD
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Cordycepin , Ca 2+ mobilization , cAMP , Inositol trisphosphate receptor , VASP , Fibrinogen binding
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