title: Increased 3-nitrotyrosine in both sporadic and familial amyotrophic lateral sclerosis.
abstract: The pathogenesis of neuronal degeneration in both sporadic and familial amyotrophic lateral sclerosis (ALS) associated with mutations in superoxide dismutase may involve oxidative stress. A leading candidate as a mediator of oxidative stress is peroxynitrite, which is formed by the reaction of superoxide with nitric oxide. 3-Nitrotyrosine is a relatively specific marker for oxidative damage mediated by peroxynitrite. In the present study, biochemical measurements showed increased concentrations of 3-nitrotyrosine and 3-nitro-4-hydroxyphenylacetic acid in the lumbar and thoracic spinal cord of ALS patients. Increased 3-nitrotyrosine immunoreactivity was observed in motor neurons of both sporadic and familial ALS patients. Neurologic control patients with cerebral ischemia also showed increased 3-nitrotyrosine immunoreactivity. These findings suggest that peroxynitrite-mediated oxidative damage may play a role in the pathogenesis of both sporadic and familial ALS.
authors.affiliation: Neurochemistry Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston 02114, USA.
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
authors.forename: R J
authors.initials: RJ
authors.lastname: Ferrante
authors.forename: S E
authors.initials: SE
authors.lastname: Browne
authors.forename: R T
authors.initials: RT
authors.lastname: Matthews
authors.forename: N W
authors.initials: NW
authors.lastname: Kowall
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D005192:Family Health; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000737:chemistry / Q000201:enzymology; D009154:Mutation; D009562:Nissl Bodies; D009596:Nitrophenols / Q000032:analysis; D018384:Oxidative Stress; D010648:Phenylacetates / Q000032:analysis; D013116:Spinal Cord / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000276:immunology / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D009596:Nitrophenols; D010648:Phenylacetates; C026242:4-hydroxy-5-nitrophenyl acetic acid; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase