Low-affinity heparin stimulates the inactivation of plasminogen activator inhibitor-1 by thrombin

Détails

ID Serval
serval:BIB_B6F46A7CAD3F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Low-affinity heparin stimulates the inactivation of plasminogen activator inhibitor-1 by thrombin
Périodique
Blood
Auteur(s)
Patston  P. A., Schapira  M.
ISSN
0006-4971 (Print)
Statut éditorial
Publié
Date de publication
08/1994
Volume
84
Numéro
4
Pages
1164-72
Notes
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Aug 15
Résumé
The influence of heparin on the reaction between thrombin and plasminogen activator inhibitor-1 (PAI-1) has been examined. With a 50-fold excess of PAI-1, the rate constant for the inhibition of thrombin was 458 mol/L-1s-1, which increased to 5,000 mol/L-1s-1 in the presence of 25 micrograms/mL unfractionated heparin or heparin with low affinity for antithrombin. The effect of low affinity heparin was then examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, using close to equimolar concentrations of reactants. Thrombin and PAI-1 formed a stable stoichiometric complex in the absence of heparin, which did not dissociate after the addition of 25 micrograms/mL low-affinity heparin. In contrast, when low-affinity heparin was added at the beginning of the reaction, there was an initial increase in PAI-1-thrombin complex formation, but this was rapidly followed by substantial proteolytic cleavage of unreacted PAI-1 and of the thrombin-PAI-1 complex. The idea that the relative concentrations of thrombin and PAI-1, and the presence of low affinity heparin, could influence the products of the reaction was examined in detail. Quantitative zymographic analysis of tissue plasminogen activator and PAI-1 activities and chromogenic substrate assay of thrombin activity showed that low-affinity heparin stimulated the inactivation of PAI-1 by an equimolar amount of thrombin, but caused only a minimal stimulation of thrombin inhibition. It is concluded that low-affinity heparin stimulates thrombin inhibition when PAI-1 is in excess, but, unexpectedly, that low-affinity heparin enhances PAI-1 inactivation when thrombin is equimolar to PAI-1.
Mots-clé
Amino Acid Sequence Electrophoresis, Polyacrylamide Gel Heparin/*pharmacology Humans Kinetics Molecular Sequence Data Oligopeptides Plasminogen Activator Inhibitor 1/isolation & purification/*metabolism Recombinant Proteins/antagonists & inhibitors/metabolism Substrate Specificity Thrombin/antagonists & inhibitors/isolation & purification/*metabolism Tissue Plasminogen Activator/metabolism Urinary Plasminogen Activator/metabolism
Pubmed
Web of science
Création de la notice
25/01/2008 16:28
Dernière modification de la notice
03/03/2018 20:46
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