title: Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase.
abstract: Cultured rat and human astrocytes and rat neurones were shown to release reduced glutathione (GSH). In addition, GSH oxidation was retarded by the concomitant release of a factor from the cells. One possibility is that this factor is extracellular superoxide dismutase (SOD). In support of this, the factor was found to bind heparin, have a molecular mass estimated to be between 50 and 100 kDa, and CuZn-type SOD protein and cyanide sensitive enzyme activity were demonstrated in the cell-conditioned medium. In addition, supplementation of native medium with exogenous CuZn-type SOD suppressed GSH oxidation. We propose that preservation of released GSH is essential to allow for maximal up-regulation of GSH metabolism in neurones. Furthermore, cytokine stimulation of astrocytes increased release of the extracellular SOD, and enhanced stability of GSH. This may be a protective strategy occurring in vivo under conditions of oxidative stress, and suggests that SOD mimetics may be of therapeutic use.
authors.affiliation: Department of Molecular Pathogenesis, Division of Neurochemistry, UCL, Institute of Neurology, London, UK.
authors.forename: Victoria C
authors.initials: VC
authors.lastname: Stewart
authors.forename: Rebecca
authors.initials: R
authors.lastname: Stone
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Gegg
authors.forename: Martyn A
authors.initials: MA
authors.lastname: Sharpe
authors.forename: Roger D
authors.initials: RD
authors.lastname: Hurst
authors.forename: John B
authors.initials: JB
authors.lastname: Clark
authors.forename: Simon J R
authors.initials: SJ
authors.lastname: Heales
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism*; D001254:Astrocytoma / Q000378:metabolism; D002478:Cells, Cultured; D002846:Chromatography, Affinity; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005110:Extracellular Space / Q000378:metabolism*; D005374:Filtration; D005978:Glutathione / Q000378:metabolism*; D006493:Heparin / Q000378:metabolism; D006801:Humans; D008970:Molecular Weight; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D006493:Heparin; D013482:Superoxide Dismutase; D005978:Glutathione