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...
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todo:paper_00493848_v120_n5_p745_Castanon2023-10-03T14:52:38Z Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators Castañon, M.M. Gamba, C. Kordich, L.C. 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 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. Fil:Castañon, M.M. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Gamba, C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Kordich, L.C. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_00493848_v120_n5_p745_Castanon |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
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 |
| spellingShingle |
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 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 |
| topic_facet |
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 |
| description |
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. |
| format |
JOUR |
| author |
Castañon, M.M. Gamba, C. Kordich, L.C. |
| author_facet |
Castañon, M.M. Gamba, C. Kordich, L.C. |
| author_sort |
Castañon, M.M. |
| title |
Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators |
| title_short |
Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators |
| title_full |
Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators |
| title_fullStr |
Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators |
| title_full_unstemmed |
Insight into the profibrinolytic activity of dermatan sulfate: Effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators |
| title_sort |
insight into the profibrinolytic activity of dermatan sulfate: effects on the activation of plasminogen mediated by tissue and urinary plasminogen activators |
| url |
http://hdl.handle.net/20.500.12110/paper_00493848_v120_n5_p745_Castanon |
| work_keys_str_mv |
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| _version_ |
1807314770676678656 |