title: Calcium-dependent free radical generation in cultured retinal neurons injured by kainate.
abstract: Cultured rat retinal neurons exposed to kainate produced free radicals, as demonstrated by electron spin resonance (ESR) spin trapping using the nitrone 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) and the generation of DMPO hydroxyl adduct (DMPO-OH). This DMPO-OH production was abolished by EGTA, nitro-arginine and oxypurinol, suggesting that it was dependent on Ca2+ influx and subsequent activation of nitric oxide synthase and xanthine oxidase. Moreover, kainate induced a receptor-mediated Ca2+ influx and neuronal injury assessed by lactate dehydrogenase release. Neuroprotection afforded by nitro-arginine and oxypurinol shows that calcium-dependent free radical production plays a major role in kainate retinal toxicity.
authors.affiliation: Laboratoire de Physiologie Cellulaire, Université Montpellier, France.
authors.forename: N
authors.initials: N
authors.lastname: Dutrait
authors.forename: M
authors.initials: M
authors.lastname: Culcasi
authors.forename: C
authors.initials: C
authors.lastname: Cazevieille
authors.forename: S
authors.initials: S
authors.lastname: Pietri
authors.forename: P
authors.initials: P
authors.lastname: Tordo
authors.forename: C
authors.initials: C
authors.lastname: Bonne
authors.forename: A
authors.initials: A
authors.lastname: Muller
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002478:Cells, Cultured; D004578:Electron Spin Resonance Spectroscopy; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D005609:Free Radicals / Q000378:metabolism*; D007608:Kainic Acid / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine; D010117:Oxypurinol / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors
chemical_list: D018690:Excitatory Amino Acid Agonists; D005609:Free Radicals; D011810:Quinoxalines; D019335:Nitroarginine; C056723:FG 9041; D001120:Arginine; D007770:L-Lactate Dehydrogenase; D019001:Nitric Oxide Synthase; D014969:Xanthine Oxidase; D010117:Oxypurinol; D007608:Kainic Acid; D002118:Calcium