title: 3-Nitropropionic acid induces apoptosis in cultured striatal and cortical neurons.
abstract: Ingestion of 3-nitropropionic acid (3-NPA) in moldy sugar cane causes brain damage in children. The mechanism of 3-NPA toxicity is thought to be inhibition of energy production, leading to ATP depletion and excitotoxicity. We exposed cultured mouse striatal or cortical neurons to 1-2 mM 3-NPA for 48 h. This exposure produced gradual neuronal degeneration characterized by cell body shrinkage and DNA fragmentation. Addition of glutamate antagonists during 3-NPA exposure did not reduce neuronal death. However, addition of the macromolecular synthesis inhibitors cycloheximide, emetine or actinomycin D markedly reduced neuronal death. Our results do not exclude that 3-NPA can induce excitotoxicity in more intact systems, but raise the additional possibility that 3-NPA may also act to induce neuronal apoptosis.
authors.affiliation: Center for the Study of Nervous System Injury, Washington University School of Medicine, St Louis, MO 63110, USA.
authors.forename: M I
authors.initials: MI
authors.lastname: Behrens
authors.forename: J
authors.initials: J
authors.lastname: Koh
authors.forename: L M
authors.initials: LM
authors.lastname: Canzoniero
authors.forename: S L
authors.initials: SL
authors.lastname: Sensi
authors.forename: C A
authors.initials: CA
authors.lastname: Csernansky
authors.forename: D W
authors.initials: DW
authors.lastname: Choi
mesh_terms: D000818:Animals; D017209:Apoptosis; D002118:Calcium; D016923:Cell Death; D002478:Cells, Cultured; D051379:Mice; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects; D011422:Propionates / Q000494:pharmacology*; D014793:Visual Cortex / Q000187:drug effects*
chemical_list: D011422:Propionates; C029658:propionic acid; D002118:Calcium