Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators
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...
Guardado en:
| Autores principales: | , , |
|---|---|
| Formato: | JOUR |
| Materias: | |
| Acceso en línea: | http://hdl.handle.net/20.500.12110/paper_00493848_v120_n5_p745_Castanon |
| Aporte de: |
| Sumario: | 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. |
|---|