Thrombin and the thrombin-thrombomodulin complex interaction with plasminogen activator inhibitor type-1
| Autor: | Renee Madden, Levin Eg, Richard A. Marlar |
|---|---|
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_treatment
Receptors Cell Surface Thrombomodulin Tissue plasminogen activator Cofactor Thrombin Fibrinolysis medicine Animals Humans chemistry.chemical_classification biology Chemistry Plasminogen Activator Inhibitor Type 1 Hematology General Medicine Kinetics Plasminogen Inactivators Enzyme biology.protein Biophysics Receptors Thrombin Rabbits Plasminogen activator circulatory and respiratory physiology medicine.drug |
| Zdroj: | Blood coagulationfibrinolysis : an international journal in haemostasis and thrombosis. 2(3) |
| ISSN: | 0957-5235 |
| Popis: | Thrombin, the final enzyme of the coagulation system, also influences profibrinolytic activity by several mechanisms. These include cellular release of tissue plasminogen activator, activated protein C-induced fibrinolysis, and inactivation of plasminogen activator inhibitor, type 1 (PAI-1). In this report, the role of thrombin in the regulation of PAI-1 is investigated. Our studies demonstrate that thrombin inactivation of PAI-1 occurs via an enzymatic mechanism rather than an enzyme-inhibitor complex mechanism. Evidence to support this conclusion is: (1) concomitant analysis of PAI-1 and thrombin activities demonstrate decreased PAI-1 activity but no loss of thrombin activity; (2) no visible thrombin--PAI-1 complexes by SDS-PAGE analysis; and (3) lack of formation of 125I-thrombin-PAI-1 complexes. Thrombomodulin, a thrombin binding cofactor that modifies thrombin's functions, did not influence the inactivation of PAI-1 by thrombin. We propose that thrombin enzymatically inactivates PAI-1 without forming a stable enzyme-inhibitor complex. The reaction is not affected by thrombomodulin. Overall this reaction occurs so slowly that it is not physiologically relevant without some modifying factor(s). |
| Databáze: | OpenAIRE |
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