Anticoagulant and antithrombotic properties of a gamma-carboxyglutamic acid-rich peptide derived from the light chain of blood coagulation factor X.

Abstract

In this report, we describe the anticoagulant and antithrombotic properties of a peptide (residues 1-44) derived from the amino-terminus of the bovine Factor X light chain by limited proteolysis with chymotrypsin, and subsequently purified by QAE-Sephadex chromatography. The effect of Factor X gla-peptide on the activation of human 3H-Factors IX and X was studied using radiometric assays and purified coagulation factors. Factor VIIa-tissue factor catalyzed activation of Factors IX and X was half-maximally inhibited by Factor X gla-peptide at concentrations of 0.8 microM and 0.2 microM, respectively. Factor IXa-VIII catalyzed Factor X activation was half-maximally inhibited at a gla-peptide concentration of 0.5 microM. In addition, thrombin formation by platelets incubated with Factor Xa and prothrombin could be similarly blocked by gla-peptide. Studies with bovine aortic endothelial cells indicated that the Factor X gla-peptide blocked in parallel Factor X binding and activation on the cell surface. Decarboxylation of the peptide by acid heat treatment destroyed its anticoagulant activity. The in vivo anticoagulant potential of native gla-peptide was demonstrated by a rapid prolongation of the PT and APTT following intravenous infusion into a rabbit. In addition, gla-peptide prevented thrombus formation in response to Factors IXa and Xa, but not thrombin, in a Wessler venous stasis model.

• Authors: P P Nawroth, W Kisiel, D M Stern
• Journal: Thrombosis research (Thromb Res) Vol. 44 Issue 5 Pg. 625-37 (Dec 01 1986) ISSN: 0049-3848 [Print] United States
• PMID: 3810564 (Publication Type: Journal Article)

Chemical References

• Anticoagulants
• Peptide Fragments
• 1-Carboxyglutamic Acid
• Prothrombin
• Factor IX
• Factor X
• Chymotrypsin

Topics

• 1-Carboxyglutamic Acid (metabolism, physiology)
• Animals
• Anticoagulants (physiology)
• Aorta (cytology)
• Blood Coagulation (drug effects)
• Cattle
• Chymotrypsin (pharmacology)
• Endothelium (drug effects)
• Factor IX (antagonists & inhibitors)
• Factor X (metabolism, physiology)
• Partial Thromboplastin Time
• Peptide Fragments (isolation & purification, physiology)
• Protein Binding
• Prothrombin (antagonists & inhibitors)
• Rabbits
• Thrombosis (prevention & control)