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Introduction: Dermatan sulfate (DS) is well-known for its anticoagulant activity through binding to heparin cofactor II to enhance antithrombin action. It has also been suggested that DS has a profibrinolytic effect, although the exact molecular mechanism is as yet unknown. Materials and methods: An in vitro amidolytic method was used to study the effect of high and low molecular weight-DS on the activation of Glu and Lys-plasminogen by tissue and urinary plasminogen activators (t-PA and u-PA). Results: Both high and low molecular weight-DS exhibited a stimulating effect on the activation of plasminogen by PAs. Interestingly, high molecular weight-DS stimulated Glu and Lys-plasminogen activation by t-PA and u-PA in a way and to an extent similar to that in which fibrin(ogen) degradation products (PDF) increased the t-PA assay. Meanwhile low molecular weight-DS had a lower effect. No DS had any effect on plasmin or u-PA amidolytic activity. The facilitation of the conversion of Glu-plasminogen to plasmin in the presence of DS was confirmed by SDS-PAGE; high molecular weight-DS effect was greater than low molecular weight-DS in accordance with the chromogenic assays. Moreover, the combination of PDF and high and low molecular weight-DS, respectively, did not further stimulate t-PA activation of either Glu or Lys-plasminogen suggesting that both substances may compete for the same binding sites. Conclusions: Through in vitro assays we demonstrated that high and low molecular weight-DS enhance plasminogen activation by u-PA and t-PA, suggesting that the profibrinolytic activity of DS might be via potentiation of plasminogen conversion to plasmin. © 2007 Elsevier Ltd. All rights reserved.


Documento: Artículo
Título:Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators
Autor:Castañon, M.M.; Gamba, C.; Kordich, L.C.
Filiación:Laboratorio de Hemostasia y Trombosis, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina
Palabras clave:Dermatan sulfate; Fibrin-fibrinogen degradation products; Plasminogen activation; Tissue plasminogen activator; Urinary plasminogen activator; dermatan sulfate; fibrin degradation product; glutamic acid; heparin cofactor II; plasmin; plasminogen; plasminogen[glutamic acid]; plasminogen[lysine]; tissue plasminogen activator; unclassified drug; urokinase; article; binding site; controlled study; enzyme activity; fibrinolysis; human; molecular weight; plasminogen activation; polyacrylamide gel electrophoresis; priority journal; protein function; reaction analysis; Anticoagulants; Antithrombins; Dermatan Sulfate; Fibrinolysis; Glutamic Acid; Humans; Hydrolysis; Models, Chemical; Molecular Weight; Peptide Fragments; Plasmin; Plasminogen; Plasminogen Activators; Time Factors; Tissue Plasminogen Activator; Urinary Plasminogen Activator
Página de inicio:745
Página de fin:752
Título revista:Thrombosis Research
Título revista abreviado:Thromb. Res.
CAS:dermatan sulfate, 24967-94-0; glutamic acid, 11070-68-1, 138-15-8, 56-86-0, 6899-05-4; heparin cofactor II, 81604-65-1; plasmin, 9001-90-5, 9004-09-5; plasminogen, 9001-91-6; tissue plasminogen activator, 105913-11-9; urokinase, 139639-24-0; Anticoagulants; Antithrombins; Dermatan Sulfate, 24967-94-0; Glutamic Acid, 56-86-0; Peptide Fragments; Plasmin,; Plasminogen, 9001-91-6; Plasminogen Activators, 3.4.21.-; Tissue Plasminogen Activator,; Urinary Plasminogen Activator,; lysyl-plasminogen


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---------- APA ----------
Castañon, M.M., Gamba, C. & Kordich, L.C. (2007) . Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators. Thrombosis Research, 120(5), 745-752.
---------- CHICAGO ----------
Castañon, M.M., Gamba, C., Kordich, L.C. "Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators" . Thrombosis Research 120, no. 5 (2007) : 745-752.
---------- MLA ----------
Castañon, M.M., Gamba, C., Kordich, L.C. "Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators" . Thrombosis Research, vol. 120, no. 5, 2007, pp. 745-752.
---------- VANCOUVER ----------
Castañon, M.M., Gamba, C., Kordich, L.C. Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators. Thromb. Res. 2007;120(5):745-752.