title: L-β-N-oxalyl-α,β-diaminopropionic acid toxicity in motor neurons.
abstract: The excitatory amino acid L-β-N-oxalyl-α,β-diaminopropionic acid (L-β-ODAP) in Lathyrus sativus L. is proposed as the causative agent of the neurodegenerative disease neurolathyrism. We investigated the effect of L-β-ODAP on [Ca2+]i handling, redox homeostasis, and cell death in rat spinal motor neurons. L-β-ODAP and L-glutamate triggered [Ca2+]i transients, which were inhibited by the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor blockers; 2,3-dioxo-6-nitro-1,2,3, 4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide and 1-naphthyl acetylspermine, the latter specifically blocking Ca2+-permeable α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors. In addition, 2,3-dioxo-6-nitro-1,2,3,4-tetrahydrobenzo[f]quinoxaline-7-sulfonamide, and to a lesser extent 1-naphthyl acetylspermine, protected the neurons against cell death induced by L-β-ODAP or L-glutamate. Methionine and cysteine were also protective against neuronal cell death. We conclude that deregulation of [Ca2+]i homeostasis and oxidative stress contribute to motor neuron cell death in neurolathyrism.
authors.affiliation: Department of Basic Medical Sciences, Physiology Group, Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium.
authors.forename: Marijke
authors.initials: M
authors.lastname: Van Moorhem
authors.forename: Elke
authors.initials: E
authors.lastname: Decrock
authors.forename: Elke
authors.initials: E
authors.lastname: De Vuyst
authors.forename: Marijke
authors.initials: M
authors.lastname: De Bock
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Fernand
authors.initials: F
authors.lastname: Lambein
authors.forename: Ludo
authors.initials: L
authors.lastname: Van Den Bosch
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D007842:Lathyrism / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D016472:Motor Neuron Disease / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051381:Rats; D015091:beta-Alanine / Q000031:analogs & derivatives* / Q000633:toxicity
chemical_list: C510363:3-N-oxalyl-L -2,3-diaminopropanoic acid; D015091:beta-Alanine