NMDA-dependent superoxide production and neurotoxicity

摘要: NEURONAL injury resulting from acute brain insults and some neurodegenerative diseases implicates N-methyl-D-aspartate (NMDA) glutamate receptors1–4. The fact that antioxidants reduce types of damage suggests oxygen radicals may have a role5–7. It has been shown mutations in Cu/Zn-superoxide dismutase (SOD), an enzyme catalysing superoxide (O·-2) detoxification the cell, are linked to familial form amyotrophic lateral sclerosis (ALS)4. Here we report O·-2 is produced upon NMDA receptor stimulation cultured cerebellar granule cells. Electron paramagnetic resonance was used assess production due part release arachidonic acid. Activation kainic acid receptors, or voltage-sensitive Ca2+ channels, did not produce detectable O·-2. We also find nitrone DMPO (5,5-dimethyl pyrroline 1-oxide), as spin trap, more efficient than nitric oxide synthase inhibitor, L-NG-nitroarginine, reducing NMDA-induced neuronal death these cultures.