Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death.

Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death. Biochim Biophys Acta. 2014 Dec 12; Authors: Ill-Raga G, Palomer E, Ramos-Fernández E, Guix FX, Bosch-Morató M, Guivernau B, Tajes M, Valls-Comamala V, Jiménez-Conde J, Ois A, Pérez-Asensio F, Reyes-Navarro M, Caballo C, Gil-Gómez G, López-Vílchez I, Galán AM, Alameda F, Escolar G, Opazo C, Planas A, Roquer J, Valverde MA, Muñoz FJ Abstract 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 human brain areas also showed that both fibrinogen and nitrotyrosinated fibrinogen spread into the brain parench...
Source: Biochimica et Biophysica Acta - Category: Biochemistry Authors: Tags: Biochim Biophys Acta Source Type: research