title: Nitro-oxidative stress after neuronal ischemia induces protein nitrotyrosination and cell death.
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.
authors: Laboratory of Molecular Physiology and Channelopathies, Universitat Pompeu Fabra, Barcelona, 08003 Catalonia, Spain.
authors: Marta
authors: M
authors: Tajes
authors: Gerard
authors: G
authors: Ill-Raga
authors: Ernest
authors: E
authors: Palomer
authors: Eva
authors: E
authors: Ramos-Fernández
authors: Francesc X
authors: FX
authors: Guix
authors: Mònica
authors: M
authors: Bosch-Morató
authors: Biuse
authors: B
authors: Guivernau
authors: Jordi
authors: J
authors: Jiménez-Conde
authors: Angel
authors: A
authors: Ois
authors: Fernando
authors: F
authors: Pérez-Asensio
authors: Mario
authors: M
authors: Reyes-Navarro
authors: Carolina
authors: C
authors: Caballo
authors: Ana M
authors: AM
authors: Galán
authors: Francesc
authors: F
authors: Alameda
authors: Ginés
authors: G
authors: Escolar
authors: Carlos
authors: C
authors: Opazo
authors: Anna
authors: A
authors: Planas
authors: Jaume
authors: J
authors: Roquer
authors: Miguel A
authors: MA
authors: Valverde
authors: Francisco J
authors: FJ
authors: Muñoz
mesh_terms: D000818:Animals; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D051379:Mice; D020030:Nitric Oxide Donors / Q000494:pharmacology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives / Q000187:drug effects
chemical_list: D020030:Nitric Oxide Donors; D011506:Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D006861:Hydrogen Peroxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
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