title: Metal-ion catalyzed oxidation affects fibrinogen activity on platelet aggregation and adhesion.
abstract: Exposure of fibrinogen to the Fe3+/ascorbate oxidative system resulted in structural modifications and altered functionality of the glycoprotein. The overnight treatment of fibrinogen by oxidants caused a 20-fold increase of carbonyl content with respect to the native protein. Formation of dityrosines as well as loss of tryptophan following fibrinogen 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 capability from the native molecule to mediate platelet aggregation and adhesion. The percentage of ADP-induced platelet aggregation decreased as a function of fibrinogen oxidative damage. Further, both unstimulated platelets and ADP-activated platelets showed a reduced ability to adhere to oxidized fibrinogen than to the native protein. These results suggest that oxidative treatment alters fibrinogen domains involved in the recognition and the binding of this molecule by the platelet receptor GP IIb/IIIa.
authors.affiliation: Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Italy.
authors.forename: M A
authors.initials: MA
authors.lastname: Belisario
authors.forename: C
authors.initials: C
authors.lastname: Di Domenico
authors.forename: A
authors.initials: A
authors.lastname: Pelagalli
authors.forename: R
authors.initials: R
authors.lastname: Della Morte
authors.forename: N
authors.initials: N
authors.lastname: Staiano
mesh_terms: D001205:Ascorbic Acid / Q000378:metabolism; D002384:Catalysis; D005290:Ferric Compounds / Q000378:metabolism* / Q000494:pharmacology; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D010084:Oxidation-Reduction / Q000187:drug effects; D010973:Platelet Adhesiveness / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology
chemical_list: D005290:Ferric Compounds; D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D001205:Ascorbic Acid