Peroxynitrite‐mediated oxidation of fibrinogen inhibits clot formation

FEBS Letters

Lupidi, G.²  Angeletti, M.²  Coletta, M.¹  Eleuteri, A.M.²  Tacconi, L.²  Fioretti, E.² 

[1] Department of Biochemical Sciences and Experimental Medicine, University of Rome ‘Tor Vergata’, Rome, Italy;Department of Molecular Cellular and Animal Biology, Postgraduate School in Clinical Biochemistry, University of Camerino, Via Camerini 2, 62032 Camerino, Italy

关键词: Fibrinogen;    Protein oxidation;    Peroxynitrite;    Clotting;   

DOI  :  10.1016/S0014-5793(99)01500-8

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 μM at 25°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.

【 授权许可】

Unknown