Nitro-oxidative stress after neuronal ischemia induces protein nitrotyrosination and cell death

Tajes Orduña, Marta; Ill-Raga, Gerard, 1982-; Palomer, Ernest; Ramos Fernández, Eva, 1984-; Guix Ràfols, Francesc Xavier; Bosch Morató, Mònica, 1986-; Guivernau Almazán, Biuse, 1988-; Jiménez Conde, Jordi; Ois Santiago, Angel Javier; Pérez Asensio, Fernando; Reyes Navarro, Mario; Caballo, Carolina; Galán, Ana M.; Alameda Quitllet, Francisco; Escolar, Ginès; Opazo, Carlos M.; Planas, Anna; Roquer, Jaume; Valverde, M. A. (Miguel Ángel), 1963-; Muñoz López, Francisco José, 1964-

doi:http://dx.doi.org/10.1155/2013/826143

Nitro-oxidative stress after neuronal ischemia induces protein nitrotyrosination and cell death

Citation

Tajes M, Ill-Raga G, Palomer E, Ramos-Fernández E, Guix FX, Bosch-Morató M et al. Nitro-oxidative stress after neuronal ischemia induces protein nitrotyrosination and cell death. Oxid Med Cell Longev. 2013;2013:826143. DOI: 10.1155/2013/826143

Abstract

Ischemic stroke is an acute vascular event that obstructs blood supply to the brain, producing irreversible damage that affects neurons but also glial and brain vessel cells. Immediately after the stroke, the ischemic tissue produces nitric oxide (NO) to recover blood perfusion but also produces superoxide anion. These compounds interact, producing peroxynitrite, which irreversibly nitrates protein tyrosines. The present study measured NO production in a human neuroblastoma (SH-SY5Y), a murine glial (BV2), a human endothelial cell line (HUVEC), and in primary cultures of human cerebral myocytes (HC-VSMCs) after experimental ischemia in vitro. Neuronal, endothelial, and inducible NO synthase (NOS) expression was also studied up to 24 h after ischemia, showing a different time course depending on the NOS type and the cells studied. Finally, we carried out cell viability experiments on SH-SY5Y cells with H2O2, a prooxidant agent, and with a NO donor to mimic ischemic conditions. We found that both compounds were highly toxic when they interacted, producing peroxynitrite. We obtained similar results when all cells were challenged with peroxynitrite. Our data suggest that peroxynitrite induces cell death and is a very harmful agent in brain ischemia.