Ukr.Biochem.J. 2014; Volume 86, Issue 5, Sep-Oct, pp. 74-81

doi: https://doi.org/10.15407/ubj86.05.074

Dynamics of thrombin-induced exposition of actin on the platelet surface

A. A. Tykhomyrov

Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: artem_tykhomyrov@ukr.net

Platelets play the key role in thrombosis and are also involved in angiogenesis as well as immune and reparative responses. In the function cascade, platelets undergo a complex cell processing, and subcellular fragments, not detectable in the resting state, are exposed on platelet surface after stimulation with agonists. This study has been performed to evaluate dynamic characteristics of actin exposition on the surface of plasma membrane of thrombin-activated platelets. Using flow-cytometric assay, it has been observed that the level of actin presented on activated platelets directly depends on agonist concentration. In the case of platelet stimulation with thrombin in the highest concentration (1.0 U/ml) taken for this study, the level of actin exposed on activated platelets was up to 4.4 times higher as compared with resting cells. Confirmation of the flow cytometry data for cell-surface actin on thrombin-activated platelets was achieved by direct visualization using a confocal laser scanning microscopy. Period of actin exposition appeared to be longer than the time phase corresponding to platelet secretion stage. Functional role of platelet surface actin has required further detailed studying, however, it is thought that superficial actin could interact with various blood plasma proteins, including plasminogen and its activators, serving as a binding site and/or center for their pericellular processing.

Keywords: , , , , ,


References:

  1. Michelson A. D. Platelets (the third edition). Academic Press, 2012. 1398 p.
  2. Hartwig JH. The platelet: form and function. Semin Hematol. 2006 Jan;43(1 Suppl 1):S94-100. Review. PubMed, CrossRef
  3. Fox JE. The platelet cytoskeleton. Thromb Haemost. 1993 Dec 20;70(6):884-93. Review. PubMed
  4. Thon JN, Italiano JE. Platelets: production, morphology and ultrastructure. Handb Exp Pharmacol. 2012;(210):3-22. Review. PubMed, CrossRef
  5. Podor TJ, Singh D, Chindemi P, Foulon DM, McKelvie R, Weitz JI, Austin R, Boudreau G, Davies R. Vimentin exposed on activated platelets and platelet microparticles localizes vitronectin and plasminogen activator inhibitor complexes on their surface. J Biol Chem. 2002 Mar 1;277(9):7529-39. Epub 2001 Dec 14. PubMed, CrossRef
  6. George JN, Lyons RM, Morgan RK. Membrane changes associated with platelet activation. Exposure of actin on the platelet surface after thrombin-induced secretion. J Clin Invest. 1980 Jul;66(1):1-9. PubMed, PubMedCentral, CrossRef
  7. Tschoepe D, Spangenberg P, Esser J, Schwippert B, Kehrel B, Roesen P, Gries FA. Flow-cytometric detection of surface membrane alterations and concomitant changes in the cytoskeletal actin status of activated platelets. Cytometry. 1990;11(5):652-6. PubMed, CrossRef
  8. Tykhomyrov A. A. Interaction of actin with plasminogen/plasmin system: mechanisms and physiological role. Biopolym Cell. 2012;28(6):413-423. CrossRef
  9. Wang H, Doll JA, Jiang K, Cundiff DL, Czarnecki JS, Wilson M, Ridge KM, Soff GA. Differential binding of plasminogen, plasmin, and angiostatin4.5 to cell surface beta-actin: implications for cancer-mediated angiogenesis. Cancer Res. 2006 Jul 15;66(14):7211-5. PubMed, CrossRef
  10. Miles LA, Andronicos NM, Baik N, Parmer RJ. Cell-surface actin binds plasminogen and modulates neurotransmitter release from catecholaminergic cells. J Neurosci. 2006 Dec 13;26(50):13017-24. PubMed, CrossRef
  11. Gear AR, Suttitanamongkol S, Viisoreanu D, Polanowska-Grabowska RK, Raha S, Camerini D. Adenosine diphosphate strongly potentiates the ability of the chemokines MDC, TARC, and SDF-1 to stimulate platelet function. Blood. 2001 Feb 15;97(4):937-45. PubMed, CrossRef
  12. Roka-Moya YM, Zhernossekov DD, Grinenko TV. Plasminogen/plasmin influence on platelet aggregation. Biopolym Cell. 2012;28(5):352-356. CrossRef
  13. Verheul HM, Lolkema MP, Qian DZ, Hilkes YH, Liapi E, Akkerman JW, Pili R, Voest EE. Platelets take up the monoclonal antibody bevacizumab. Clin Cancer Res. 2007 Sep 15;13(18 Pt 1):5341-7. Epub 2007 Sep 12. PubMed, CrossRef
  14. Por SB, Cooley MA, Breit SN, Penny R, French PW. Antibodies to tubulin and actin bind to the surface of a human monocytic cell line, U937. J Histochem Cytochem. 1991 Jul;39(7):981-5. PubMed, CrossRef
  15. Bachvaroff RJ, Miller F, Rapaport FT. Appearance of cytoskeletal components on the surface of leukemia cells and of lymphocytes transformed by mitogens and Epstein-Barr virus. Proc Natl Acad Sci U S A. 1980 Aug;77(8):4979-83. PubMed, PubMedCentral, CrossRef
  16. De Candia E. Mechanisms of platelet activation by thrombin: a short history. Thromb Res. 2012 Mar;129(3):250-6. Epub 2011 Dec 2. Review. PubMedCrossRef
  17. Stalker TJ, Newman DK, Ma P, Wannemacher KM, Brass LF. Platelet signaling. Handb Exp Pharmacol. 2012;(210):59-85. Review. PubMed, CrossRef
  18. Smalheiser NR. Proteins in unexpected locations. Mol Biol Cell. 1996 Jul;7(7):1003-14. Review. PubMed, PubMedCentral, CrossRef
  19. Arnoys EJ, Wang JL. Dual localization: proteins in extracellular and intracellular compartments. Acta Histochem. 2007;109(2):89-110. Epub 2007 Jan 25. Review. PubMed, CrossRef
  20. Owen MJ, Auger J, Barber BH, Edwards AJ, Walsh FS, Crumpton MJ. Actin may be present on the lymphocyte surface. Proc Natl Acad Sci U S A. 1978 Sep;75(9):4484-8. PubMed, PubMedCentral, CrossRef
  21. Gousset K, Wolkers WF, Tsvetkova NM, Oliver AE, Field CL, Walker NJ, Crowe JH, Tablin F. Evidence for a physiological role for membrane rafts in human platelets. J Cell Physiol. 2002 Jan;190(1):117-28. PubMed, CrossRef
  22. Klement GL, Yip TT, Cassiola F, Kikuchi L, Cervi D, Podust V, Italiano JE, Wheatley E, Abou-Slaybi A, Bender E, Almog N, Kieran MW, Folkman J. Platelets actively sequester angiogenesis regulators. Blood. 2009 Mar 19;113(12):2835-42. Epub 2008 Nov 25. PubMed, PubMedCentral, CrossRef
  23. Jurasz P, Alonso D, Castro-Blanco S, Murad F, Radomski MW. Generation and role of angiostatin in human platelets. Blood. 2003 Nov 1;102(9):3217-23. Epub 2003 Jul 10. PubMed, CrossRef
  24. Jurasz P, Santos-Martinez MJ, Radomska A, Radomski MW. Generation of platelet angiostatin mediated by urokinase plasminogen activator: effects on angiogenesis. J Thromb Haemost. 2006 May;4(5):1095-106. PubMed, CrossRef
  25. Radziwon-Balicka A., Moncada de la Rosa C., Zielnik B., Doroszko A., Jurasz P. Temporal and pharmacological characterization of angiostatin release and generation by human platelets: implications for endothelial cell migration. PLoS One. 2013;8(3):e59281.  PubMedPubMedCentralCrossRef
  26. Liu DY, Clarke GN, Baker HW. Exposure of actin on the surface of the human sperm head during in vitro culture relates to sperm morphology, capacitation and zona binding. Hum Reprod. 2005 Apr;20(4):999-1005. Epub 2005 Jan 13. PubMed, CrossRef

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