Prothrombinase acceleration by oxidatively damaged phospholipids.
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.
Weinstein
E A
EA
Department of Pharmacology and Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Li
H
H
Lawson
J A
JA
Rokach
J
J
FitzGerald
G A
GA
Axelsen
P H
PH
D007700:Kinetics; D013058:Mass Spectrometry; D008563:Membrane Lipids / Q000378:metabolism*; D010084:Oxidation-Reduction; D010743:Phospholipids / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism*
D008563:Membrane Lipids; D010743:Phospholipids; D013925:Thromboplastin