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Inhibitory Effects of PD98059, SB203580, and SP600125 on α-and δ-granule Release and Intracellular Ca2+ Levels in Human Platelets

  • Kwon, Hyuk-Woo (Department of Biomedical Laboratory Science, Far East University)
  • Received : 2018.05.28
  • Accepted : 2018.08.29
  • Published : 2018.09.30

Abstract

Platelets are activated at sites of vascular injury via several molecules, such as adenosine diphosphate, collagen and thrombin. Full platelet aggregation is absolutely essential for normal hemostasis. Moreover, this physiological event can trigger circulatory disorders, such as thrombosis, atherosclerosis, and cardiovascular disease. Therefore, platelet function inhibition is a promising approach in preventing platelet-mediated circulatory disease. Many studies reported the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in platelet functions. However, these studies were limited. Thus, we examined MAPK signaling pathways in human platelets using specific MAPK inhibitors, such as PD98059, SB203580, and SP600125. We observed that these inhibitors were involved in calcium mobilization and influx in human platelets. They also suppressed thrombin-induced ${\alpha}$- and ${\delta}$-granule release. These results suggest that PD98059, SB203580, and SP600125 exhibit $Ca^{2+}$ antagonistic effects.

Keywords

References

  1. Adam F, Kauskot A, Nurden P, Sulpice E, Hoylaerts MF, Davis RJ, Bryckaert M. Platelet JNK1 is involved in secretion and thrombus formation. Blood. 2010. 115: 4083-4092. https://doi.org/10.1182/blood-2009-07-233932
  2. Adam F, Kauskot A, Rosa JP, Bryckaert M. Mitogen-activated protein kinases in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis. 2008. 6: 2007-2016. https://doi.org/10.1111/j.1538-7836.2008.03169.x
  3. Berridge MJ, Irvine RF. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature. 1984. 312: 315-321. https://doi.org/10.1038/312315a0
  4. Borsch-Haubold AG, Kramer RM, Watson SP. Cytosolic phospholipase $A_{2}$ is phosphorylated in collagen-and thrombinstimulated human platelets independent of protein kinase C and mitogen-activated protein kinase. Journal of Biological Chemistry. 1995. 270: 25885-25892. https://doi.org/10.1074/jbc.270.43.25885
  5. Borsch-Haubold AG, Kramer RM, Watson SP. Inhibition of mitogenactivated protein kinase kinase does not impair primary activation of human platelets. Biochemical Journal. 1996. 318: 207-212. https://doi.org/10.1042/bj3180207
  6. Borsch-Haubold AG, Pasquet S, Watson SP. Direct inhibition of cyclooxygenase-1 and-2 by the kinase inhibitors SB 203580 and PD 98059 SB 203580 also inhibits thromboxane synthase. Journal of Biological Chemistry. 1998. 273: 28766-28772. https://doi.org/10.1074/jbc.273.44.28766
  7. Bugaud F, Nadal-Wollbold F, Levy-Toledano S, Rosa JP, Bryckaert M. Regulation of c-jun-NH2 terminal kinase and extracellularsignal regulated kinase in human platelets. Blood. 1999. 94: 3800-3805.
  8. Cattaneo M. The P2 receptors and congenital platelet function defects. In Seminars in thrombosis and hemostasis. 2005. 31: 168-173. https://doi.org/10.1055/s-2005-869522
  9. Elvers M, Herrmann A, Seizer P, Munzer P, Beck S, Schonberger T, Gawaz M. Intracellular cyclophilin A is an important $Ca^{2+}$ regulator in platelets and critically involved in arterial thrombus formation. Blood. 2012. 120: 1317-1326. https://doi.org/10.1182/blood-2011-12-398438
  10. Grynkiewicz G, Poenie M, Tsien RY. A new generation of $Ca^{2+}$ indicators with greatly improved fluorescence properties. Journal of Biological Chemistry. 1985. 260: 3440-3450.
  11. Guidetti GF, Lova P, Bernardi B, Campus F, Baldanzi G, Graziani A, Balduini C, Torti M. The Gi-coupled P2Y12 receptor regulates diacylglycerol-mediated signaling in human platelets. Journal of Biological Chemistry. 2008. 283: 28795-28805. https://doi.org/10.1074/jbc.M801588200
  12. Jennings LK. Role of platelets in atherothrombosis. The American Journal of Cardiology. 2009. 103: 4A-10A.
  13. Kaibuchi K, Sano K, Hoshijima M, Takai Y, Nishizuka Y. Phosphatidy linositol turnover in platelet activation; calcium mobilization and protein phosphorylation. Cell Calcium. 1982. 3: 323-335. https://doi.org/10.1016/0143-4160(82)90020-3
  14. Kramer RM, Roberts EF, Strifler BA, Johnstone EM. Thrombin induces activation of p38 MAP kinase in human platelets. Journal of Biological Chemistry. 1995. 270: 27395-27398. https://doi.org/10.1074/jbc.270.46.27395
  15. Kramer RM, Roberts EF, Um SL, Borsch-Haubold AG, Watson SP, Fisher MJ, Jakubowski JA. p38 mitogen-activated protein kinase phosphorylates cytosolic phospholipase $A_{2}$ (cPLA2) in thrombin-stimulated platelets Evidence that proline-directed phosphorylation is not required for mobilization of arachidonic acid by cPLA2. Journal of Biological Chemistry. 1996. 271: 27723-27729. https://doi.org/10.1074/jbc.271.44.27723
  16. Kyriakis JM, App H, Zhang XF, Banerjee P, Brautigan DL, Rapp UR, Avruch J. Raf-1 activates MAP kinase-kinase. Nature. 1992. 358: 417-421. https://doi.org/10.1038/358417a0
  17. Lang F, Munzer P, Gawaz M, Borst O. Regulation of STIM1/Orai1-dependent $Ca^{2+}$ signalling in platelets. Thrombosis and Hhaemostasis. 2013. 110: 925-930. https://doi.org/10.1160/TH13-02-0176
  18. Lopez E, Jardin I, Berna-Erro A, Bermejo N, Salido GM, Sage SO, Redondo PC. STIM1 tyrosine-phosphorylation is required for STIM1-Orai1 association in human platelets. Cellular Signalling. 2012. 24: 1315-1322. https://doi.org/10.1016/j.cellsig.2012.02.012
  19. Nadal-Wollbold F, Pawlowski M, Levy-Toledano S, Berrou E, Rosa JP, Bryckaert M. Platelet ERK2 activation by thrombin is dependent on calcium and conventional protein kinases C but not Raf-1 or B-Raf. FEBS Letters. 2002. 531: 475-482. https://doi.org/10.1016/S0014-5793(02)03587-1
  20. Nishikawa M, Tanaka T, Hidaka H. $Ca^{2+}$-calmodulin dependent phosphorylation and platelet secretion. Nature. 1980. 287: 863-865. https://doi.org/10.1038/287863a0
  21. Pozo-Guisado E, Casas-Rua V, Tomas-Martin P, Lopez-Guerrero AM, Alvarez-Barrientos A, Martin-Romero FJ. Phosphorylation of STIM1 at ERK1/2 Target sites regulates the interaction with the microtubule plus-end binding protein EB1. J Cell Sci. 2013. 126: 3170-3180. https://doi.org/10.1242/jcs.125054
  22. Quinton TM, Dean WL. Cyclic AMP-dependent phosphorylation of the inositol-1,4,5-trisphosphate receptor inhibits $Ca^{2+}$ release from platelet membranes. Biochemical and Biophysical Research Communications. 1992. 184: 893-899. https://doi.org/10.1016/0006-291X(92)90675-B
  23. Ramakrishnan V, DeGuzman F, Bao M, Hall SW, Leung LL, Phillips DR. A thrombin receptor function for platelet glycoprotein Ib-IX unmasked by cleavage of glycoprotein V. Proceedings of the National Academy of Sciences of the United States of America. 2001. 98: 1823-1828. https://doi.org/10.1073/pnas.98.4.1823
  24. Shin JH, Kwon HW, Cho HJ, Rhee MH, Park HJ. Inhibitory effects of total saponin from Korean Red Ginseng on $[Ca^{2+}]_i$ mobilization through phosphorylation of cyclic adenosine monophosphate-dependent protein kinase catalytic subunit and inositol 1, 4, 5-trisphosphate receptor type I in human platelets. Journal of Ginseng Research. 2015. 39: 354-364. https://doi.org/10.1016/j.jgr.2015.03.006
  25. van Blesen T, Hawes BE, Luttrell DK, Krueger KM, Touhara K, Porfflri E, Lefkowitz RJ. Receptor-tyrosine-kinase-and $G{\beta}{\gamma}$-mediated MAP kinase activation by a common signalling pathway. Nature. 1995. 376: 781-784. https://doi.org/10.1038/376781a0
  26. Varga-Szabo D, Braun A, Nieswandt B. Calcium signaling in platelets. Journal of Thrombosis and Haemostasis. 2009. 7: 1057-1066. https://doi.org/10.1111/j.1538-7836.2009.03455.x
  27. Yacoub D, Theoret JF, Villeneuve L, Abou-Saleh H, Mourad W, Allen BG, Merhi Y. Essential role of protein kinase $C{\delta}$ in platelet signaling, ${\alpha}IIb{\beta}3$ activation, and thromboxane $A_{2}$ release. Journal of Biological Chemistry. 2006. 281: 30024-30035. https://doi.org/10.1074/jbc.M604504200