Preservation of extracellular glutathione by an astrocyte derived factor with properties comparable to extracellular superoxide dismutase.
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.
Stewart
Victoria C
VC
Department of Molecular Pathogenesis, Division of Neurochemistry, UCL, Institute of Neurology, London, UK.
Stone
Rebecca
R
Gegg
Matthew E
ME
Sharpe
Martyn A
MA
Hurst
Roger D
RD
Clark
John B
JB
Heales
Simon J R
SJ
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
D017077:Culture Media, Conditioned; D016207:Cytokines; D006493:Heparin; D013482:Superoxide Dismutase; D005978:Glutathione