title: Pyruvate protects motor neurons expressing mutant superoxide dismutase 1 against copper toxicity.
abstract: Mutations in the copper/zinc superoxide dismutase (SOD1) gene are known to be responsible for familial amyotrophic lateral sclerosis. Alteration of metal binding properties of mutant SOD1 has been proposed to play a role in the pathogenesis of amyotrophic lateral sclerosis. We investigated the toxic effects of excess extracellular copper on motor neuronal cells expressing human mutant SOD1 (G93A), and evaluated the neuroprotective effects of energy metabolism intermediates or cofactors. Motoneuron-neuroblastoma hybrid (VSC 4.1) cells expressing mutant SOD1, when treated with copper chloride, showed reduced viability and increased levels of endogenous peroxides. Moreover, this copper-induced toxicity was attenuated by a free radical scavenger, a caspase inhibitor, or a calpain inhibitor. Of the energy metabolism intermediates examined, pyruvate significantly reduced the death and production of reactive oxygen species in cells expressing mutant SOD1. Our data suggest that pyruvate could be of therapeutic value in some forms of familial amyotrophic lateral sclerosis.
authors.affiliation: Department of Neurology, Seoul National University College of Medicine, Clinical Research Institute of Seoul National University Hospital, Chongnoku, Seoul 110-744, Korea.
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Kim
authors.forename: Jong-Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Jong-Ha
authors.initials: JH
authors.lastname: Park
authors.forename: Jung-Joon
authors.initials: JJ
authors.lastname: Sung
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Kwang-Woo
authors.initials: KW
authors.lastname: Lee
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003300:Copper / Q000633:toxicity*; D004734:Energy Metabolism / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D006822:Hybrid Cells; D009046:Motor Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D009154:Mutation; D009447:Neuroblastoma; D018696:Neuroprotective Agents / Q000494:pharmacology; D019289:Pyruvic Acid / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013831:Thiamine / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology
chemical_list: D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; C000606290:SOD1 protein, human; D008063:Thioctic Acid; D003300:Copper; D019289:Pyruvic Acid; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D013831:Thiamine