These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Low-affinity heparin stimulates the inactivation of plasminogen activator inhibitor-1 by thrombin.
    Author: Patston PA, Schapira M.
    Journal: Blood; 1994 Aug 15; 84(4):1164-72. PubMed ID: 8049432.
    Abstract:
    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.
    [Abstract] [Full Text] [Related] [New Search]