Superoxide-induced nitric oxide release from cultured glial cells

• Published in: Brain research 2001-08, Vol.911 (2), p.203-210
• Main Authors: Manning, Philip, Cookson, Mark R, McNeil, Calum J, Figlewicz, Denise, Shaw, Pamela J
• Format: Article
• Language: English
• Subjects: Animals; Astrocyte; Astrocytes - cytology; Astrocytes - drug effects; Astrocytes - metabolism; Benzoates - pharmacology; Biological and medical sciences; Extracellular Space - drug effects; Extracellular Space - metabolism; Free radical; Free Radical Scavengers - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Genetic Vectors; Imidazoles - pharmacology; Isolated neuron and nerve. Neuroglia; Metalloporphyrins - pharmacology; Nerve Degeneration - metabolism; Nerve Degeneration - physiopathology; Neurodegeneration; Neurodegenerative Diseases - metabolism; Neurodegenerative Diseases - physiopathology; Neurons - drug effects; Neurons - metabolism; Nitric Oxide - metabolism; Nitric oxide synthase; Nitric Oxide Synthase - drug effects; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Oxidative Stress - drug effects; Oxidative Stress - physiology; Rats; RNA, Messenger - drug effects; RNA, Messenger - metabolism; Superoxide Dismutase - genetics; Superoxide Dismutase - metabolism; Superoxide Dismutase-1; Superoxides - metabolism; Transfection; Tumor Cells, Cultured - cytology; Tumor Cells, Cultured - drug effects; Tumor Cells, Cultured - metabolism; Vertebrates: nervous system and sense organs; Xanthine - metabolism; Xanthine Oxidase - pharmacology
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(01)02688-9

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.