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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2015; 61(6): 26-34


A.A. Tykhomyrov, D.D. Zhernosekov, Y.M. Roka-Moya, S.I. Diordieva, T.V. Grinenko

    Palladin Institute of Biochemistry of National Academy of Sciences of Ukraine, Kyiv


The effects of Lys- plasminogen on platelet α-granule secretion were studied. The level of P-selectin exposed on the surface of plasma membranes of washed human platelets was measured by flow cytometry as a marker of α-granule secretion. It was shown that Lys- plasminogen facilitates partial release of α-granules, but impedes thrombin-induced platelet exocytosis. It is suggested that Lys- plasminogen may affect platelet secretion rather through interaction of its non-catalytic (kringle) domains with membrane receptors than due to contaminating plasmin activity. In contrast to Lys-form, native proenzyme (Glu-plasminogen) had no effects on α-granule releasing. Here, we provide the first experimental demonstration that Lys-form of plasminogen is able to modulate platelet α-granule secretion, and this effect can be considered as one of the plausible mechanisms of its anti-aggregating activity.

Keywords: platelets; platelet secretion; α-granules; P-selectin; plasminogen; flow cytometry.


  1. Law RH, Abu-Ssaydeh D, Whisstock JC. New insights into the structure and function of the plasminogen/plasmin system. Curr Opin Struct Biol. 2013; 23(6): 836-41. CrossRef PubMed
  3. Zhernosekov DD, Iusova EI, Grinenko TV. Role of plasminogen/plasmin in functional activity of blood cells. Ukr Biokhim Zh. 2012; 84(4): 5-19. [Russian].
  5. Miles LA, Castellino FJ, Gong Y. Critical role for conversion of Glu-plasminogen to Lys-plasminogen for optimal stimulation of plasminogen activation on cell surfaces. Trends Cardiovasc Med. 2003; 13(1): 21-30. CrossRef  
  6. Gong Y, Kim SO, Felez J, Grella DK, Castellino FJ, Miles LA. Conversion of Glu-plasminogen to Lys-plasminogen is necessary for optimal stimulation of plasminogen activation on the endothelial cell surface. J Biol Chem. 2001; 276(22): 19078-83. CrossRef PubMed
  8. Zhang L, Gong Y, Grella DK, Castellino FJ, Miles LA. Endogenous plasmin converts Glu-plasminogen to Lysplasminogen on the monocytoid cell surface. J Thromb Haemost. 2003; 1(6): 1264-70. CrossRef PubMed
  10. Miles LA, Plow EF. Binding and activation of plasminogen on the platelet surface. J Biol Chem. 1985; 260(7): 4303-11.
  12. Baeten KM, Richard MC, Kanse SM, Mutch NJ, Degen JL, Booth NA. Activation of single-chain urokinase-type plasminogen activator by platelet-associated plasminogen: a mechanism for stimulation of fibrinolysis by platelets. J Thromb Haemost. 2010; 8(6): 1313-22. CrossRef PubMed
  14. Roka-Moya YM, Zhernossekov DD, Grinenko TV. Plasminogen/plasmin influence on platelet aggregation. Biopolymers and Cell. 2012; 28(5): 352-356. [Ukrainian].
  16. Tykhomyrov AO, Zhernosiekov DD, Roka-Moia IaM, Diordiieva SI, Hrynenko TV. Effects of Lys-form of plasminogen on platelet actin cytoskeleton. Fiziol Zh. 2014; 60(1): 25-33. (in Ukrainian)
  18. Flaumenhaft R, Dilks JR, Rozenvayn N, MonahanEarley RA, Feng D, Dvorak AM. The actin cytoskeleton differentially regulates platelet alpha-granule and densegranule secretion. Blood. 2005; 105(10): 3879-87. CrossRef PubMed
  20. Andre P. P-selectin in haemostasis. Br J Haematol. 2004; 126(3): 298-306. CrossRef PubMed
  22. Michelson AD. Evaluation of platelet function by flow cytometry. Pathophysiol Haemost Thromb. 2006; 35(1- 2): 67-82.
  24. Kim PY, Tieu LD, Stafford AR, Fredenburgh JC, Weitz JI. A high affinity interaction of plasminogen with fibrin is not essential for efficient activation by tissue-type plasminogen activator. J Biol Chem. 2012; 287(7): 4652-61. CrossRef PubMed PubMedCentral
  26. Kinlough-Rathbone RL, Perry DW, Rand ML, Packham MA. Pretreatment of human platelets with plasmin inhibits responses to thrombin, but potentiates responses to low concentrations of aggregating agents, including the thrombin receptor activating peptide, SFLLRN. Thromb Haemost. 1997; 77(4): 741-7.
  28. Leytin V, Mody M, Semple JW, Garvey B, Freedman J. Quantification of platelet activation status by analyzing P-selectin expression. Biochem Biophys Res Commun. 2000; 273(2): 565-70. CrossRef PubMed
  30. Shigeta O, Kojima H, Jikuya T, Terada Y, Atsumi N, Sakakibara Y, Nagasawa T, Mitsui T. Aprotinin inhibits plasmin-induced platelet activation during cardiopulmonary bypass. Circulation. 1997; 96(2): 569-74. CrossRef PubMed
  32. Quinton TM, Kim S, Derian CK, Jin J, Kunapuli SP. Plasmin-mediated activation of platelets occurs by cleavage of protease-activated receptor 4. J Biol Chem. 2004; 279(18): 18434-9. CrossRef PubMed
  34. Holvoet P, Lijnen HR, Collen D. A monoclonal antibody specific for Lys-plasminogen. Application to the study of the activation pathways of plasminogen in vivo. J Biol Chem. 1985; 260(22): 12106-11.
  36. Silverstein RL, Friedlander RJ Jr, Nicholas RL, Nachman RL. Binding of Lys-plasminogen to monocytes/ macrophages. J Clin Invest. 1988; 82(6): 1948-55. CrossRef PubMed PubMedCentral
  38. Hajjar KA, Nachman RL. Endothelial cell-mediated conversion of Glu-plasminogen to Lys-plasminogen. Further evidence for assembly of the fibrinolytic system on the endothelial cell surface. J Clin Invest. 1988; 82(5): 1769-78. CrossRef PubMed PubMedCentral
  40. Woronowicz K, Dilks JR, Rozenvayn N, Dowal L, Blair PS, Peters CG, et al. The platelet actin cytoskeleton associates with SNAREs and participates in alpha-granule secretion. Biochemistry. 2010; 49(21): 4533-42. CrossRef PubMed PubMedCentral
  42. Natarajan P, May JA, Sanderson HM, Zabe M, Spangenberg P, Heptinstall S. Effects of cytochalasin H, a potent inhibitor of cytoskeletal reorganisation, on platelet function. Platelets. 2000; 11(8): 467-76. CrossRef PubMed
  44. Merten M, Thiagarajan P. P-selectin expression on platelets determines size and stability of platelet aggregates. Circulation. 2000; 102(16): 1931-6. CrossRef PubMed
  46. Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci U S A. 1995; 92(16): 7450-4. CrossRef PubMed PubMedCentral

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