Superoxide-induced nitric oxide release from cultured glial cells.
Nitric oxide (NO) has been implicated as a potential contributor to neural cell death in a variety of neurological conditions. Cultured glial cells were exposed to extracellular superoxide generated by the action of xanthine oxidase on xanthine. In this experimental paradigm, both C6 glioma cells and primary astrocytes from rat cerebral cortex produced a rapid release of nitric oxide, measured using an NO specific electrode, in response to the applied superoxide stimulus. Application of a superoxide scavenger, or over-expression of Cu/Zn superoxide dismutase decreased the observed NO release. Authenticity of the NO signal was confirmed by the addition of the NO scavenger 2-(carboxyphenyl)-4,4,5,5-tetramethyllimidazoline-1-oxyl 3-oxide (carboxy-PTIO), which abolished the observed NO release without affecting simultaneously measured superoxide. Therefore, we suggest that glial cells may produce NO under free radical stimulation, which may be relevant to several neurological disorders where superoxide radicals are generated in the vicinity of glia. This would be predicted to result in the release of NO, which may exert toxic effects on neighbouring cells.
Manning
P
P
Department of Clinical Biochemistry, The Medical School, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, UK.
Cookson
M R
MR
McNeil
C J
CJ
Figlewicz
D
D
Shaw
P J
PJ
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001565:Benzoates / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D005822:Genetic Vectors; D007093:Imidazoles / Q000494:pharmacology; D008665:Metalloporphyrins / Q000494:pharmacology; D009410:Nerve Degeneration / Q000378:metabolism / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D000072105:Superoxide Dismutase-1; D013481:Superoxides / Q000378:metabolism*; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D019820:Xanthine / Q000378:metabolism; D014969:Xanthine Oxidase / Q000494:pharmacology
D001565:Benzoates; D016166:Free Radical Scavengers; D007093:Imidazoles; D008665:Metalloporphyrins; D012333:RNA, Messenger; C097284:manganese(III)-tetrakis(4-benzoic acid)porphyrin; D013481:Superoxides; C079393:1,3-dihydroxy-4,4,5,5-tetramethyl-2-(4-carboxyphenyl)tetrahydroimidazole; D019820:Xanthine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D014969:Xanthine Oxidase