Acceleration of the thrombin inactivation of single chain urokinase-type plasminogen activator (pro-urokinase) by thrombomodulin
| Autor: | G.A.W. de Munk, E. Groeneveld, D. C. Rijken |
|---|---|
| Přispěvatelé: | Instituut voor Verouderings- en Vaatziekten Onderzoek TNO |
| Jazyk: | angličtina |
| Rok vydání: | 1991 |
| Předmět: |
medicine.medical_treatment
Endothelial cells Receptors Cell Surface Thrombomodulin Kringle domain Thrombin Fibrinolysis medicine Humans Support Non-U.S. Gov't Polyacrylamide gel electrophoresis Biology Urokinase General Medicine Urokinase-Type Plasminogen Activator Molecular biology Thrombolytic therapy Molecular Weight Kinetics Biochemistry cardiovascular system Urinary Plasminogen Activator Calcium Receptors Thrombin Plasminogen activator Fetomodulin Protein C Research Article medicine.drug Human |
| Zdroj: | Journal of Clinical Investigation, 5, 88, 1680-1684 |
| Popis: | The in vitro effects of thrombomodulin on the inactivation of single chain urokinase-type plasminogen activator (scu-PA) by thrombin were investigated by incubating scu-PA with varying concentrations of human thrombin, in both the absence and presence of soluble rabbit thrombomodulin. 50% inactivation of scu-PA occurred in 45 min at 160 ng/ml thrombin in the absence of thrombomodulin and at 4.6 ng/ml thrombin in the presence of thrombomodulin. No difference was found in either the absence or the presence of thrombomodulin between the inactivation rates of high molecular weight scu-PA, and a low molecular weight scu-PA which lacked the growth factor and kringle domains. Enzyme kinetic experiments with varying concentrations of scu-PA showed that thrombomodulin decreased the K(m) of thrombin for scu-PA from 7.8 to 0.43 μM and increased the k(cat) from 0.30 to 1.2 s-1, corresponding to a 70-fold increase in the second-order rate constant k(cat)/K(m)·SDS- polyacrylamide gel electrophoresis showed that scu-PA was cleaved into two chains upon inactivation by thrombin, and confirmed the acceleration effect of thrombomodulin on inactivation of scu-PA. Thrombomodulin thus not only has anticoagulant properties but is also antifibrinolytic. The acceleration may imply a new mechanism for the regulation of local plasminogen activator activity on the cell surface. |
| Databáze: | OpenAIRE |
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