title: Prothrombinase acceleration by oxidatively damaged phospholipids.
abstract: The optimally efficient production of thrombin by the prothrombinase complex relies on suitable positioning of its component factors and substrate on phosphatidylserine-containing lipid membranes. The presence of oxidatively damaged phospholipids in a membrane disrupts the normal architecture of a lipid bilayer and might therefore be expected to interfere with prothrombinase activity. To investigate this possibility, we prepared phosphatidylserine-containing lipid vesicles containing oxidized arachidonoyl lipids, and we examined their ability to accelerate thrombin production by prothrombinase. Oxidized arachidonoyl chains caused dose-dependent increases in prothrombinase activity up to 6-fold greater than control values. These increases were completely attenuated by the presence of alpha-tocopherol, gamma-tocopherol, or ascorbate. Over the course of a 300-min oxidation, the ability of arachidonoyl lipids to accelerate prothrombinase peaked at 60 min and then declined to base-line levels. These results suggest that instead of being impeded by oxidative membrane damage, prothrombinase activity is enhanced by one or more products of nonenzymatic lipid oxidation.
authors.affiliation: Department of Pharmacology and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: E A
authors.initials: EA
authors.lastname: Weinstein
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: J A
authors.initials: JA
authors.lastname: Lawson
authors.forename: J
authors.initials: J
authors.lastname: Rokach
authors.forename: G A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: P H
authors.initials: PH
authors.lastname: Axelsen
mesh_terms: D007700:Kinetics; D013058:Mass Spectrometry; D008563:Membrane Lipids / Q000378:metabolism*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
chemical_list: D008563:Membrane Lipids; D010743:Phospholipids; D013925:Thromboplastin