Calcium-dependent free radical generation in cultured retinal neurons injured by kainate.
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.
Dutrait
N
N
Laboratoire de Physiologie Cellulaire, Université Montpellier, France.
Culcasi
M
M
Cazevieille
C
C
Pietri
S
S
Tordo
P
P
Bonne
C
C
Muller
A
A
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
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