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PubMed · 7687749

NMDA-dependent superoxide production and neurotoxicity.

M Lafon-Cazal·S Pietri·M Culcasi·J Bockaert
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Abstract

Neuronal injury resulting from acute brain insults and some neurodegenerative diseases implicates N-methyl-D-aspartate (NMDA) glutamate receptors. The fact that antioxidants reduce some types of brain damage suggests that oxygen radicals may have a role. It has been shown that mutations in Cu/Zn-superoxide dismutase (SOD), an enzyme catalysing superoxide (O2.-) detoxification in the cell, are linked to a familial form of amyotrophic lateral sclerosis (ALS). Here we report that O2.- is produced upon NMDA receptor stimulation in cultured cerebellar granule cells. Electron paramagnetic resonance was used to assess O2.- production that was due in part to the release of arachidonic acid. Activation of kainic acid receptors, or voltage-sensitive Ca2+ channels, did not produce detectable O2.-. We also find that the nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), used as a spin trap, is more efficient than the nitric oxide synthase inhibitor, L-NG-nitro-arginine, in reducing NMDA-induced neuronal death in these cultures.

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Amino Acid OxidoreductasesAnimalsArachidonic AcidArginineCalcium ChannelsCell DeathCells, CulturedCerebral CortexComputer SimulationCyclic N-OxidesElectron Spin Resonance SpectroscopyMiceNitric Oxide SynthaseNitroarginineQuinacrineReceptors, GlutamateKainic Acid ReceptorsReceptors, N-Methyl-D-AspartateSuperoxide DismutaseSuperoxidesXanthineXanthine OxidaseXanthinesJournal ArticleResearch Support, Non-U.S. Gov't

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M Lafon-Cazal, S Pietri, M Culcasi, J Bockaert. 1993-08-05. NMDA-dependent superoxide production and neurotoxicity.. https://doi.org/10.1038/364535a0

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