METAL-ION CATALYZED OXIDATION AFFECTS FIBRINOGEN ACTIVITY ON PLATELET-AGGREGATION AND ADHESION

Exposure of fibrinogen to the Fe3+/ascorbate oxidative system resulted in structural modifications and altered functionality of the glycopro tein. The overnight treatment of fibrinogen by oxidants caused a 20-fo ld increase of carbonyl content with respect to the native protein. Fo rmation of dityrosines as well as loss of tryptophan following fibrino gen oxidation were observed. The occurrence of conformational changes of the fibrinogen molecule as a consequence of the oxidative treatment was also established. Oxidized fibrinogen showed a distinct capabilit y from the native molecule to mediate platelet aggregation and adhesio n. The percentage of ADP-induced platelet aggregation decreased as a f unction of fibrinogen oxidative damage. Further, both unstimulated pla telets and ADP-activated platelets showed a reduced ability to adhere to oxidized fibrinogen than to the native protein. These results sugge st that oxidative treatment alters fibrinogen domains involved in the recognition and the binding of this molecule by the platelet receptor GP IIb/IIIa.