title: Nitrotyrosination contributes minimally to toxicity of mutant SOD1 associated with ALS.
abstract: Enhanced production of nitrotyrosine and subsequent protein nitration has been proposed as the mechanism by which mutant SOD1 causes death of motor neurons in a familial form of amyotrophic lateral sclerosis (FALS-1). We have tested this hypothesis in a primary culture model in which mutant human SOD1 was expressed in motor neurons of dissociated spinal cord cultures. Preventing formation of nitrotyrosine by inhibiting nitric oxide synthase rescued cultured motor neurons from excitotoxic death induced by adding glutamate to the culture medium, but failed to significantly delay death of motor neurons expressing the G93A mutant SOD1. The results do not support generation of nitrotyrosine being the predominant lethal gain of function conferred by mutations in SOD1.
authors.affiliation: Montreal Neurological Institute and Department of Neurology/Neurosurgery, McGill University, 3801 University St., Montreal, QC, Canada H3A 2B4.
authors.forename: M M
authors.initials: MM
authors.lastname: Doroudchi
authors.forename: S
authors.initials: S
authors.lastname: Minotti
authors.forename: D A
authors.initials: DA
authors.lastname: Figlewicz
authors.forename: H D
authors.initials: HD
authors.lastname: Durham
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology* / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D006801:Humans; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism*; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; C002744:3-nitrotyrosine; D018698:Glutamic Acid; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D019331:NG-Nitroarginine Methyl Ester