Insight into the profibrinolytic activity of dermatan sulfate: effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators.
BACKGROUND
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.


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.
Castañon
María Mercedes
MM
Laboratorio de Hemostasia y Trombosis, Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina. mamecas@qb.fcen.uba.ar
Gamba
Cecilia
C
Kordich
Lucía C
LC
D000925:Anticoagulants / Q000378:metabolism; D000991:Antithrombins / Q000378:metabolism; D003871:Dermatan Sulfate / Q000737:chemistry / Q000494:pharmacology*; D005341:Fibrinolysin / Q000378:metabolism; D005342:Fibrinolysis / Q000187:drug effects*; D018698:Glutamic Acid / Q000737:chemistry; D006801:Humans; D006868:Hydrolysis; D008956:Models, Chemical; D008970:Molecular Weight; D010446:Peptide Fragments / Q000737:chemistry; D010958:Plasminogen / Q000737:chemistry; D010960:Plasminogen Activators / Q000378:metabolism; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000378:metabolism; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism
D000925:Anticoagulants; D000991:Antithrombins; D010446:Peptide Fragments; C018998:lysyl-plasminogen; D003871:Dermatan Sulfate; D018698:Glutamic Acid; D010958:Plasminogen; D010960:Plasminogen Activators; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator