Specific glycosaminoglycans support the inhibition of thrombin by plasminogen activator inhibitor 1
| Autor: | Koen Mertens, Raymond Klein Gebbink, Craig H. Reynolds, Hans Pannekoek, Douglas M. Tollefsen |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Keratan sulfate
Thrombin Heparin Heparan sulfate Biochemistry Molecular biology Dermatan sulfate carbohydrates (lipids) Kinetics chemistry.chemical_compound chemistry Spectrophotometry Plasminogen activator inhibitor-1 Plasminogen Activator Inhibitor 1 medicine Humans Chondroitin Electrophoresis Polyacrylamide Gel Plasminogen activator Glycosaminoglycans Protein Binding medicine.drug |
| Zdroj: | Biochemistry. 32:1675-1680 |
| ISSN: | 1520-4995 0006-2960 |
| DOI: | 10.1021/bi00057a035 |
| Popis: | In the absence of accessory components, plasminogen activator inhibitor 1 (PAI-1) rapidly forms equimolar, inactive complexes both with tissue-type (t-PA) and with urokinase-type (u-PA) plamsinogen activator. In the presence of either the glycoprotein vitronectin or the glycosaminoglycan heparin, PAI-1 is endowed with additional, efficient thrombin-inhibitory properties (Ehrlich et al., 1990, 1991a). Here, we have investigated the interaction between PAI-1, thrombin, and glycosaminoglycans in more detail. Inhibition of thrombin by PAI-1 was quantitatively analyzed in the presence of a wide range of concentrations of heparin, heparan sulfate, dermatan sulfate, chondroitin 4-sulfate, chondroitin 6-sulfate, keratan sulfate, and hyaluronic acid by measuring residual amidolytic activity. In addition, a qualitative analysis was performed by determining the formation of SDS-stable, equimolar complexes between thrombin and PAI-1 in the presence of various glycosaminoglycans. Heparin, at concentrations between 0.1 and 1 microgram/mL, significantly promoted thrombin inhibition by PAI-1 as well as SDS-stable complex formation. Suboptimal inhibition was observed with dermatan sulfate, chondroitin 4-sulfate, and heparan sulfate at concentrations that are at least 1 order of magnitude higher than that required for optimal inhibition in the presence of heparin. Virtually no inhibition of thrombin and SDS-stable complex formation was detected with any of the other glycosaminoglycans at concentrations between 0.1 and 1 microgram/mL.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Databáze: | OpenAIRE |
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