title: Superoxide dismutase activity, oxidative damage, and mitochondrial energy metabolism in familial and sporadic amyotrophic lateral sclerosis.
abstract: The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is unknown. Recently, it was found that some patients with autosomal-dominant familial ALS (FALS) have point mutations in the gene that encodes Cu/Zn superoxide dismutase (SOD1). In this study of postmortem brain tissue, we examined SOD activity and quantified protein carbonyl groups, a marker of oxidative damage, in samples of frontal cortex (Brodmann area 6) from 10 control patients, three FALS patients with known SOD1 mutations (FALS-1), one autosomal-dominant FALS patient with no identifiable SOD1 mutations (FALS-O), and 11 sporadic ALS (SALS) patients. Also, we determined the activities of components of the electron transport chain (complexes I, II-III, and IV) in these samples. The cytosolic SOD activity, which is primarily SOD1 activity, was reduced by 38.8% (p < 0.05) in the FALS-1 patients and not significantly altered in the SALS patients or the FALS-O patient relative to the control patients. The mitochondrial SOD activity, which is primarily SOD2 activity, was not significantly altered in the FALS-1, FALS-O, or SALS patients. The protein carbonyl content was elevated by 84.8% (p < 0.01) in the SALS patients relative to the control patients. Finally, the complex I activity was increased by 55.3% (p < 0.001) in the FALS-1 patients relative to the control patients. These results from cortical tissue demonstrate that SOD1 activity is reduced and complex I activity is increased in FALS-1 patients and that oxidative damage to proteins is increased in SALS patients.
authors.affiliation: Neurochemistry Laboratory, Massachusetts General Hospital, Boston 02114.
authors.forename: A C
authors.initials: AC
authors.lastname: Bowling
authors.forename: J B
authors.initials: JB
authors.lastname: Schulz
authors.forename: R H
authors.initials: RH
authors.lastname: Brown
authors.forename: M F
authors.initials: MF
authors.lastname: Beal
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D001344:Autopsy; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004579:Electron Transport; D004734:Energy Metabolism; D005190:Family; D005260:Female; D005799:Genes, Dominant; D006801:Humans; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D010085:Oxidative Phosphorylation; D012016:Reference Values; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
chemical_list: D013482:Superoxide Dismutase; D002950:Citrate (si)-Synthase