Tag Archives: Glu- and Lys-plasminogen
Plasminogen influence on the PAI-1 release by human platelets
O. I. Yusova*, T. V. Grinenko, T. F. Drobot’ko, A. O. Tykhomyrov
Department of Enzyme Chemistry and Biochemistry, Palladin Institute of Biochemistry,
National Academy of Sciences of Ukraine, Kyiv;
*e-mail: yusova07@gmail.com
Received: 06 February 2024; Revised: 27 March 2024;
Accepted: 31 May 2024; Available on-line: 17 June 2024
РАІ-1 (plasminogen activator inhibitor type 1), as a major physiological inhibitor of tissue plasminogen activator and urokinase, plays a key role in the regulation of fibrinolysis in vivo. Besides, PAI-1 suppresses plasmin formation and affects cell migration through interaction with vitronectin. РАІ-1 is secreted from α-granules of platelets upon stimulation of cells by agonists. The aim of our study was to explore the effects of Glu- and Lys-forms of plasminogen on PAI-1 secretion by platelets and to evaluate the possible role of plasminogen in modulation of agonist-induced PAI-1 release. The secretion of PAI-1 by platelets was investigated by the Western blot analysis. It has been established that depending on the agonist, PAI-1 can be released from platelets in a free form, in a complex with a tissue plasminogen activator, as well as in the form of high-molecular complexes that contain a tissue activator and vitronectin molecules. The revealed induction of PAI-1 secretion under the action of Gly- and Lys-forms of plasminogen indicates their ability to activate intracellular signaling pathways that regulate the release of platelet α-granules. Our findings may be of importance for elucidating the pathogenetic mechanisms of many diseases associated with abnormally enhanced platelet function and PAI-1-related disorders.
Glu- and Lys-forms of plasminogen differentially affect phosphatidylserine exposure on the platelet surface
D. D. Zhernossekov, Y. M. Roka-Moiia, A. O. Tykhomyrov,
M. M. Guzyk, T. V. Grinenko
Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
e-mail: chemikdd@mail.ru
Plasminogen/plasmin system is known for its ability to support hemostatic balance of blood. However, plasminogen may be considered as an adhesive ligand and in this way could affect the functioning of blood cells. We showed that exogenous Lys-plasminogen, but not its Glu-form, inhibited platelet aggregation and suppressed platelet α-granule secretion. The aim of this work was to investigate the influence of Glu- and Lys-form of plasminogen on the formation of platelet procoagulant surface using phosphatidylserine exposure as a marker. Human platelets were obtained from human platelet-rich plasma (donors were healthy volunteers, men aged 30-40 years) by gel-filtration on Sepharose 2B. Phosphatidylserine exposure on the platelet surface was evaluated by flow cytometry with FITC-conjugated annexin A5. Glu- and Lys-plasminogen have different impact on the platelet functioning. Exogenous Lys-plasminogen has no significant effect on phosphatidylserine exposure, while Glu-plasminogen increases phosphatidylserine exposure on the surface of thrombin- and collagen-activated human platelets. Glu-plasminogen can be considered as a co-stimulator of agonist-induced platelet secretion and procoagulant surface formation. Meanwhile effects of Lys-plasminogen are probably directed at platelet-platelet interactions and not related to agonist-stimulated pro-apoptotic changes. The observed different effects of Glu- and Lys-plasminogen on phosphatidylserine exposure can be explained by their structural peculiarities.