Journal of Applied Biological Chemistry

  • 제62권4호
  • /
  • Pages.425-431
  • /
  • 2019
  • /
  • 1976-0442(pISSN)
  • /
  • 2234-7941(eISSN)
한국응용생명화학회 (The Korean Society for Applied Biological Chemistry)
권호 표지
DOI QR코드

DOI QR Code

Antiplatelet effects of scoparone through up-regulation of cAMP and cGMP on U46619-induced human platelets

  • Lee, Dong-Ha (Department of Biomedical Laboratory Science, Namseoul University)
  • 투고 : 2019.10.10
  • 심사 : 2019.11.14
  • 발행 : 2019.12.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A2, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP3R by scoparone resulted in inhibition of Ca2+ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.

키워드

참고문헌

  1. Furuichi T, Mikoshiba K (1995) Inositol 1, 4, 5-trisphosphate receptormediated $Ca{2+}$ signaling in the brain. J Neurochem 64: 953-960 https://doi.org/10.1046/j.1471-4159.1995.64030953.x
  2. Ohkubo S, Nakahata N, Ohizumi Y (1996) Thromboxane A2-mediated shape change: independent of Gq-phospholipase C--$Ca{2+}$ path- way in rabbit platelets. Br J Pharmacol 117: 1095-1104 https://doi.org/10.1111/j.1476-5381.1996.tb16702.x
  3. Saitoh M, Naka M, Hidaka H (1986) The modulatory role of myosin light chain phosphorylation in human platelet activation. Biochem Biophys Res Commun 140: 280-287 https://doi.org/10.1016/0006-291X(86)91087-9
  4. Cattanco M, Tenconi PM, Lecchi A, Mannucci PM (1991) In vitro effects of picotamide on human platelet aggregation, the release reaction and thromboxane B2 production. Thromb Res 62: 717-724 https://doi.org/10.1016/0049-3848(91)90375-7
  5. Su CY, Shiao MS, Wang CT (1999) Differential effects of ganodermic acid S on the thromboxane A2-signaling pathways in human platelets. Biochem Pharmacol 58: 587-595 https://doi.org/10.1016/S0006-2952(99)00136-7
  6. Menshikov MYU, Ivanova K, Schaefer M, Drummer C, Gerzer R (1993) Influence of the cGMP analog 8-PCPT-cGMP 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
  7. Schwarz UR, Walter U, Eigenthaler M (2001) Taming platelets with cyclic nucleotides. Biochem Pharmacol 62: 1153-1161 https://doi.org/10.1016/S0006-2952(01)00760-2
  8. Cavallini L, Coassin M, Borean A, Alexandre A (1996) Prostacyclin and sodium nitroprusside inhibit the activity of the platelet inositol 1,4,5-trisphosphate receptor and promote its phosphorylation. J Biol Chem 271: 5545-5551 https://doi.org/10.1074/jbc.271.10.5545
  9. Quinton TM, Dean WL (1992) Cyclic AMP-dependent phosphorylation of the inositol-1,4,5-trisphosphate receptor inhibits $Ca{2+}$ release from platelet membranes. Biochemical and Biochem Biophys Res Commun 184: 893-899 https://doi.org/10.1016/0006-291X(92)90675-B
  10. Laurent V, Loisel TP, Harbeck B, Wehman A, Grobe L, Jockusch BM, Wehland J, Gertler FB, Carlier MF (1999) Role of proteins of the Ena/VASP family in actin-based motility of Listeria monocytogenes. J Cell Biol 144: 1245-1258 https://doi.org/10.1083/jcb.144.6.1245
  11. Sudo T, Ito H, Kimura Y (2003) Phosphorylation of the vasodilatorstimulated phosphoprotein (VASP) by the anti-platelet drug, cilostazol, in platelets. Platelets 14: 381-390 https://doi.org/10.1080/09537100310001598819
  12. Huang HC, Chu SH, Chao PD (1991) Vasorelaxants from Chinese herbs, emodin and scoparone, possess immunosuppressive properties. European Journal of Pharmacology 198: 211-213 https://doi.org/10.1016/0014-2999(91)90624-Y
  13. Huang HC, Lee CR, Weng YI, Lee MC, Lee YT (1992) Vasodilator effect of scoparone (6,7-dimethoxycoumarin) from a Chinese herb. European Journal of Pharmacology 218: 123-128 https://doi.org/10.1016/0014-2999(92)90155-W
  14. Shin JH, Kwon HW, Lee DH (2019) Ginsenoside F4 inhibits platelet aggregation and thrombus formation by dephosphorylation of IP3RI and VASP. J Appl Biol Chem 62: 93-100 https://doi.org/10.3839/jabc.2019.014
  15. Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of $Ca{2+}$ indicators with greatly improved fluorescence properties. J Biol Chem 260: 3440-3450 https://doi.org/10.1016/S0021-9258(19)83641-4
  16. Berridge MJ, Irvine RF (1989) Inositol phosphates and cell signalling. Nature 341: 197-205 https://doi.org/10.1038/341197a0
  17. Nishikawa M, Tanaka T, Hidaka H (1980) $Ca{2+}$-calmodulin-dependent phosphorylation and platelet secretion. Nature 287: 863-865 https://doi.org/10.1038/287863a0
  18. Kuo JF, Andersson RG, Wise BC, Mackerlova L, Salomonsson I, Brackett NL, Katoh N, Shoji M, Wrenn RW (1980) Calcium-dependent protein kinase: widespread occurrence in various tissues and phyla of the animal kingdom and comparison of effects of phospholipid, calmodulin, and trifluoperazine. Proc Natl Acad Sci 77: 7039-7043 https://doi.org/10.1073/pnas.77.12.7039
  19. Wangorsch G, Butt E, Mark R, Hubertus K, Geiger J, Dandekar T, Dittrich M (2011) Time-resolved in silico modeling of finetuned cAMP signaling in platelets: feedback loops, titrated phosphorylations and pharmacological modulation, BMC Syst Biol 5: 178 https://doi.org/10.1186/1752-0509-5-178
  20. Napenas J, Oost FC, DeGroot A, Loven B, Hong CH, Brennan MT, Lockhart PB, van Diermen DE (2013) Review of postoperative bleeding risk in dental patients on antiplatelet therapy. Oral Surg Oral Med Oral Pathol Oral Radiol 115: 491-499 https://doi.org/10.1016/j.oooo.2012.11.001
  21. Topol EJ, Byzova TV, Plow EF (1999) Platelet GPIIb-IIIa blockers. The Lancet 353: 227-231 https://doi.org/10.1016/S0140-6736(98)11086-3
  22. Choi BR, Kim HK, Park JK (2017) Penile Erection Induced by Scoparone from Artemisia capillaris through the Nitric Oxide-Cyclic Guanosine Monophosphate Signaling Pathway. World J Mens Health 35: 196-204 https://doi.org/10.5534/wjmh.17023
  23. Gao J, Tao J, Liang W, Zhao M, Du X, Cui S, Duan H, Kan B, Su X, Jiang Z (2015) Identification and characterization of phosphodiesterases that specifically degrade 3'3'-cyclic GMP-AMP. Cell Res 25: 539-550 https://doi.org/10.1038/cr.2015.40
  24. Haslam RJ, Dickinson NT, Jang EK (1999) Cyclic nucleotides and phosphodiesterases in platelets. Thromb Haemost 82: 412 -423 https://doi.org/10.1055/s-0037-1615861

피인용 문헌

  1. Inhibitory effects of scoparone through regulation of PI3K/Akt and MAPK on collagen-induced human platelets vol.63, pp.2, 2020, https://doi.org/10.3839/jabc.2020.018