IMPAIRED CLOT LYSIS BY rt-PA CATALYZED MINI-PLASMINOGEN ACTIVATION

The fibrinolytic system contains a proenzyme plasminogen (Plg) which is converted to plasmin (Plm) by the action of Plg activators. Physiological Plg activators are: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator. Plg was shown to be further cleaved by leukocyte el...

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Bibliographic Details
Published in:	Thrombosis research Vol. 86; no. 6; pp. 505 - 513
Main Authors:	Duboscq, Cristina, Genoud, Valeria, Parborell, M.Fernanda, Kordich, Lucía C.
Format:	Journal Article
Language:	English
Published:	New York, NY Elsevier Ltd 15-06-1997 Elsevier Science
Subjects:	Biological and medical sciences Blood coagulation. Blood cells Fibrin - metabolism Fibrin - pharmacology Fibrinolysin - metabolism fibrinolysis Fibrinolysis - drug effects Fibrinolysis - physiology Fundamental and applied biological sciences. Psychology General aspects, investigation methods, hemostasis, fibrinolysis human neutrophil elastase Humans In Vitro Techniques mini-Plasminogen Molecular and cellular biology Peptide Fragments - drug effects Peptide Fragments - metabolism Plasminogen - drug effects Plasminogen - metabolism Recombinant Proteins - pharmacology Tissue Plasminogen Activator - metabolism Tissue Plasminogen Activator - pharmacology fibrinolysis mini-Plasminogen human neutrophil elastase Leukocyte elastase Peptidases Serine endopeptidases Enzyme Peptide fragment Hydrolases Plasminogen Recombinant protein Fibrinolysis t-Plasminogen activator
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Summary:	The fibrinolytic system contains a proenzyme plasminogen (Plg) which is converted to plasmin (Plm) by the action of Plg activators. Physiological Plg activators are: tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator. Plg was shown to be further cleaved by leukocyte elastase producing several fragments, one of wich is called mini-plasminogen (mini-Plg) or neo-plasminogen Val 442. In this paper we studied whether mini-Plg is able to produce clot lysis when it is activated by rt-PA in purified systems and in Plg depleted normal plasma. We found that mini-Plg clot lysis time was longer than that of Plg. Clot lysis times were 2.3 minutes ± 0.06 for Plg and 9.8 minutes ± 0.1 for mini-Plg. Mini-Plg is less efficient than Plg in producing clot lysis at all studied concentrations (0.1–1.2μM). In Plg depleted normal human plasma mini-Plg is unable to produce complete clot lysis in presence of rt-PA. Although mini-Plg can be activated to mini-Plm by rt-PA, these results show that the activation process is insufficient to produce an efficient clot lysis. © 1997 Elsevier Science Ltd
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0049-3848 1879-2472
DOI:	10.1016/S0049-3848(97)00099-6