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Information × Registration Number 0218U000719, 0113U003203 , R & D reports Title Mechanisms of plasminogen/plasmin regulation of intermolecular and intercellular interactions in the haemostasis system in norm and at a pathology. popup.stage_title Head Grinenko Tatyana Victorovna, Доктор біологічних наук Registration Date 12-02-2018 Organization A.V.Palladin Institute of Biochemistry of National Academy of Sciences popup.description2 Object of study - proteolytic plasminogen/plasmin system, which is responsible for fibrin deposition dissolution in circulation and participate in wide range of biological processes in organism regulating functional activity of cells. Aim of study - investigation of regulation mechanisms of intermolecular and intercellular interactions in hemostasis system including plasminogen/plasmin system proteins. Next tasks were set as study directions: investigation of fibrin structure changes role in plasminogen system activation, exploration of mechanisms of platelets functional state regulation by plasminogen/plasmin system, determination of blood cells effect on anticoagulant proteases activity and development of methods for the evaluation of plasminogen/plasmin system components as prognostic markers of pathologies range. Methods of study: chromatography, immune-enzyme assay, western-blot analysis, electrophoresis, flow cytometry, spectrophotometry, turbidimetry, aggregometry, protein chemistry and enzymology methods. It was demonstrated that plasminogen activation by tissue-type plasminogen activator triggered by fibrin polymerization depends on covalent cross-linking of ??-chains and Са2+-coiled coil anchor destruction in ?-subdomain of fibrin D-domain, which happen during protofibrills formation and "B'-"b" polymerization sites interaction. Binding sites for plasminogen kringle 5 were localized in ? and ? chains of fibrin. Obtained result is promising assumption for search of new approaches of fibrin clots dissolution rate regulation. Using flow cytometry and enzymatic activity assay plasminogen ability to interact with isolated platelets after their agonist-stimulated activation was demonstrated. Ability of Glu-plasminogen adsorbed on thrombin-activated platelets surface to transform into Lys-plasminogen by the action of plasmin, formed by endogenous activators was confirmed. It was established that thrombin-stimulated platelets accelerate plasminogen activation by tissue type plasminogen activator. Kinetic parameters of this process were calculated. Lys-plasminogen ability to counteract thrombin- and collagen-induced reorganization of platelet actin cytoskeleton and to inhibit agonist-induced P-selectin and VEGF secretion have shown. Demonstrated modulation of platelets functional state by plasminogen/plasmin system can be directed to angiogenesis and thrombi formation processes. On the base of obtained data test-system for plasminogen evaluation in blood plasma and method of tissue-type activity assessment in biological samples were developed and patented. Product Description popup.authors Діордієва С.А. Корса В.В. Л.Г. Капустяненко Паталах І.І. Ревка О.В. Рибачук В.Н. Рока-Мойя Я.М. Савчук О.В. Тихомиров А.О. Харченко С.М. Шкрабак М.О. Юсова О.І. Юсова О.І. Яценко Т.А. popup.nrat_date 2020-04-02 Close