Inhibitory Effects of Cordycepin (3'-Deoxyadenosine), a Component of Cordyceps militaris, on Human Platelet Aggregation Induced by Thapsigargin

  • Cho, Hyun-Jeong (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Cho, Jae-Youl (School of Bioscience and Biotechnology, Kangwon National University) ;
  • Rhee, Man-Hee (Department of Physiology, College of Veterinary Medicine, Kyungpook National University) ;
  • Kim, Hyeong-Soo (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Lee, Hyun-Sub (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University) ;
  • Park, Hwa-Jin (Department of Biomedical Laboratory Science, College of Biomedical Science and Engineering, and Regional Research Center, Inje University)
  • 발행 : 2007.07.31

초록

Cordycepin (3'-deoxyadenosine) is an adenosine analog, isolated from Cordyceps militaris, and it has been used as an anticancer and anti-inflammation ingredient in traditional Chinese medicine. We investigated the effects of cordycepin (3'-deoxyadenosine) on human platelet aggregation, which was induced by thapsigargin, a tumor promoter, and determined the cytosolic free $Ca^{2+}$ levels ($[Ca^{2+}]_i$) (an aggregation-stimulating molecule) and cyclic-guanosine monophosphate (cGMP) (an aggregation-inhibiting molecule). Cordycepin inhibited thapsigargin-induced platelet aggregation in a dose-dependent manner, and it clearly reduced the levels of $[Ca^{2+}]_i$, which was increased by thapsigargin ($1\;{\mu}M$) or U46619 ($3\;{\mu}M$). Cordycepin also increased the thapsigargin-reduced cGMP levels. Accordingly, our data demonstrated that cordycepin may have a beneficial effect on platelet aggregation-mediated thrombotic diseases through the $[Ca^{2+}]_i$-regulating system such as cGMP.

키워드

참고문헌

  1. Cunningham, K. G, W. Manson, F. S. Spring, and S. A. Hutchinson. 1950. Cordycepin, a metabolic product isolated from cultures of Cordyceps militaris (Linn.) Link. Nature 166: 949
  2. Furuichi, T. and K. Mikoshiba. 1995. Inositol 1, 4, 5-triphosphate receptor-mediated $Ca^{2+}$ signaling in the brain. J. Neurochem. 64: 953-960 https://doi.org/10.1046/j.1471-4159.1995.64030953.x
  3. Hashimoto, Y., T. Watanabe, M. Kinoshita, K. Tsukamoto, M. Togo, Y. Horie, Y. Matsuda, and K. Kurokawa. 1993. $Ca^{2+}$ entry pathways activated by the tumor promoter thapsigargin in human platelets. Biochim. Biophys. Acta 1220: 37-41 https://doi.org/10.1016/0167-4889(93)90094-6
  4. Haslam, R. J, M. M. Davidson, and J. V. Desjardins. 1978. Inhibition of adenylate cyclase by adenosine analogues in preparations of broken and intact human platelets. Evidence for the unidirectional control of platelet function by cyclic AMP. Biochem. J. 176: 83-95 https://doi.org/10.1042/bj1760083
  5. Hubbell, H. R., E. C. Pequignot, D. H. Willis, C. Lee, and R. J. Suhadolnik. 1985. Differential antiproliferative actions of 2',5' oligo A trimer core and its cordycepin analogue on human tumor cells. Int. J. Cancer 36: 389-394 https://doi.org/10.1002/ijc.1985.36.3.389
  6. Jackson, T. R., S. I. Patterson, O. Thastrup, and M. R. Hanley. 1988. A novel tumour promoter, thapsigargin, transiently increases cytoplasmic free $Ca^{2+}$ without generation of inositol phosphates in NG115-401L neuronal cells. Biochem. J. 253: 81-86
  7. Jang, E. K., J. E. Azzam, N. T. Dickinson, M. M. Davidson, and R. J. Haslam. 2002. Roles for both cyclic GMP and cyclic AMP in the inhibition of collagen-induced platelet aggregation by nitroprusside. Br. J. Haematol. 117: 664-675 https://doi.org/10.1046/j.1365-2141.2002.03479.x
  8. Kaibuchi, K., K. Sano, M. Hoshijima, Y. Takai, and Y. Nishizuka. 1982. Phosphatidylinositol turnover in platelet activation; calcium mobilization and protein phosphorylation. Cell Calcium 3: 323-335 https://doi.org/10.1016/0143-4160(82)90020-3
  9. Londos, C. and J. Wolff. 1977. Two distinct adenosinesensitive sites on adenylate cyclase. Proc. Natl. Acad. Sci. USA 74: 5482-5486
  10. Menshikov, M., K. Ivanova, M. Schaefer, C. Drummer, and R. Gerzer. 1993. Influence of the cGMP analog 8-PCPTcGMP on agonist-induced increases in cytosolic ionized $Ca^{2+}$ and on aggregation of human platelets. Eur. J. Pharmacol. 245: 281-284 https://doi.org/10.1016/0922-4106(93)90108-L
  11. Sage, S. O., P. Sargeant, J. E. Merritt, M. P. Mahaut-Smith, and T. J. Rink. 1992. Agonist-evoked $Ca^{2+}$ entry in human platelets. Biochem. J. 285: 341-344 https://doi.org/10.1042/bj2850341
  12. Saxena, S. P., A. McNicol, A. B. Becker, L. J. Brandes, O. Thastrup, and J. M. Gerrard. 1992. Biochemical and ultrastructural studies suggest that the effects of thapsigargin on human platelets are mediated by changes in intracellular calcium but not by intracellular histamine. Thromb. Haemost. 68: 714-718 https://doi.org/10.1055/s-0038-1646349
  13. Schaeffer, J. and M. P. Blaustein. 1989. Platelet free calcium concentrations measured with fura-2 are influenced by the transmembrane sodium gradient. Cell Calcium 10: 101-113 https://doi.org/10.1016/0143-4160(89)90050-X
  14. Schwartz, S. M., R. L. Heimark, and M. W. Majesky. 1990. Developmental mechanisms underlying pathology of arteries. Physiol. Rev. 70: 1177-1209 https://doi.org/10.1152/physrev.1990.70.4.1177
  15. Son, D. J., Y. H. Park, Y. M. Kim, N. H. Chung, and H. S. Lee. 2005. Antiplatelet activity of Thujopsis dolabrata var. hondai-derived component against platelet aggregation. J. Microbiol. Biotechnol. 15: 425-427
  16. Wang, G. R., Y. Zhu, P. V. Halushka, T. M. Lincoln, and M. E. Mendelsohn. 1998. Mechanism of platelet inhibition by nitric oxide: In vivo phosphorylation of thromboxane receptor by cyclic GMP-dependent protein kinase. Proc. Natl. Acad. Sci. USA 95: 4888-4893
  17. Won, S. Y. and E. H. Park. 2005. Anti-inflammatory and related pharmacological activities of cultured mycelia and fruiting bodies of Cordyceps militaris. J. Ethnopharmacol. 96: 555-561 https://doi.org/10.1016/j.jep.2004.10.009
  18. Xu, B., A. Stephens, G. Kirschenheuter, A. F. Greslin, X. Cheng, J. Sennelo, M. Cattaneo, M. L. Zighetti, A. Chen, S. A. Kim, H. S. Kim, N. Bischotberger, G. Cook, and K. A. Jacobson. 2002. Acyclic analogues of adenosine bisphosphates as P2Y receptor antagonists: Phosphate substitution leads to multiple pathways of inhibition of platelet aggregation. J. Med. Chem. 45: 5694-5709 https://doi.org/10.1021/jm020173u
  19. Yang, B. K., J. Y. Ha, S. C. Jong, S. Das, J. W. Yun, Y. S. Lee, J. W. Choi, and C. H. Song. 2000. Production of exopolymers by submerged mycelial culture of Cordyceps militaris and its hypolipidemic effect. J. Microbiol. Biotechnol. 10: 784-788
  20. Yu, K. W, H. J. Suh, S. H. Bae, C. S. Lee, S. H. Kim, and C. S. Yoon. 2001. Chemical properties and physiological activities of stromata of Cordyceps militaris. J. Microbiol. Biotechnol. 11: 266-274
  21. Yu, R., L. Song, Y. Zhao, W. Bin, L. Wang, H. Zhang, Y. Wu, W. Ye, and X. Yao. 2004. Isolation and biological properties of polysaccharide CPS-1 from cultured Cordyceps militaris. Fitoterapia 75: 465-472 https://doi.org/10.1016/j.fitote.2004.04.003