Journal article

Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death

Gerard Ill-Raga, Ernest Palomer, Eva Ramos-Fernandez, Francesc X Guix, Monica Bosch-Morato, Biuse Guivernau, Marta Tajes, Victoria Valls-Comamala, Jordi Jimenez-Conde, Angel Ois, Fernando Perez-Asensio, Mario Reyes-Navarro, Carolina Caballo, Gabriel Gil-Gomez, Irene Lopez-Vilchez, Ana M Galan, Francesc Alameda, Gines Escolar, Carlos Opazo, Anna M Planas Show all

Biochimica et Biophysica Acta (BBA) - Lipids and Lipid Metabolism | ELSEVIER SCIENCE BV | Published : 2015

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 nitrotyrosi..

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Grants

Awarded by Spanish Ministry of Science and Innovation


Awarded by Fondo de Investigacion Sanitaria


Awarded by Generalitat de Catalunya


Awarded by Fundacio la Marato de TV3


Funding Acknowledgements

This work was supported by the Spanish Ministry of Science and Innovation (SAF2012-38140; SAF 2009-10365); Fondo de Investigacion Sanitaria (FIS PI13/00408, FIS PI13/00864, CPO4-00112, PS09/00664 and Red HERACLES RD12/0042/0014, RD12/0042/0016 and RD12/0042/0020); FEDER Funds; Generalitat de Catalunya (SGRO9-1369); and Fundacio la Marato de TV3 (100310). Dr. A.M. Galan belongs to the Miguel Servet stabilization program of the Spanish Government's ISCIII research institute and "Direccio d'Estrategia i Coordinacio del Departament de Salut" of the Generalitat de Catalunya. We acknowledge Eva Gimenez for her technical support in this study.