Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death

Publication date: Available online 12 December 2014 Source:Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease Author(s): Gerard ILL-Raga , Ernest Palomer , Eva Ramos-Fernández , Francesc X. Guix , Mònica Bosch-Morató , Biuse Guivernau , Marta Tajes , Victòria Valls-Comamala , Jordi Jiménez-Conde , Angel Ois , Fernando Pérez-Asensio , Mario Reyes-Navarro , Carolina Caballo , Gabriel Gil-Gómez , Irene López-Vílchez , Ana M. Galán , Francesc Alameda , Ginés Escolar , Carlos Opazo , Anna Planas , Jaume Roquer , Miguel A. Valverde , Francisco J. Muñoz Ischemic stroke is an acute vascular event that compromises neuronal viability, and identification of the pathophysiological mechanisms is critical for its correct management. Ischemia produces increased nitric oxide synthesis to recover blood flow but also induces a free radical burst. Nitric oxide and superoxide anion react to generate peroxynitrite that nitrates tyrosines. We found that fibrinogen nitrotyrosination was detected in plasma after the initiation of ischemic stroke in human patients. Electron microscopy and protein intrinsic fluorescence showed that in vitro nitrotyrosination of fibrinogen affected its structure. Thromboelastography showed that initially fibrinogen nitrotyrosination retarded clot formation but later made the clot more resistant to fibrinolysis. This result was independent of any effect on thrombin production. Immunofluorescence analysis of affected h...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research