Peroxynitrite-mediated oxidation of fibrinogen inhibits clot formation.
The clotting activity of human fibrinogen was fully inhibited in vitro by peroxynitrite. The decrease of activity followed an exponential function and the concentration of peroxynitrite needed to inhibit 50% of fibrinogen clotting was 22 microM at 25 degrees C. The oxidative modification(s) induced by the peroxynitrite system (i.e. ONOO-, ONOOH and ONOOH*) appeared specifically to affect fibrin clot formation (through the inhibition of fibrinogen polymerization) since the interaction of peroxynitrite-modified fibrinogen with thrombin appeared to be unaffected. The addition of NaHCO3 decreased the peroxynitrite effect on fibrinogen clotting, suggesting that the reactive species formed by the reaction of CO2 with peroxynitrite are less efficient oxidants of peroxynitrite itself. Similar effects were observed after addition of bilirubin, which also exerted a significant protection against peroxynitrite-mediated modification of fibrinogen.
Lupidi
G
G
Department of Molecular Cellular and Animal Biology, Postgraduate School in Clinical Biochemistry, University of Camerino, Italy. g.lupidi@cambio.unicam.it
Angeletti
M
M
Eleuteri
A M
AM
Tacconi
L
L
Coletta
M
M
Fioretti
E
E
D001663:Bilirubin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology*; D002245:Carbon Dioxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D009566:Nitrates / Q000378:metabolism / Q000494:pharmacology*; D010084:Oxidation-Reduction; D013917:Thrombin / Q000494:pharmacology; D013997:Time Factors
D009566:Nitrates; D002245:Carbon Dioxide; C039642:peroxynitric acid; D005340:Fibrinogen; D013917:Thrombin; D001663:Bilirubin