title: Astrocytes protect against copper-catalysed loss of extracellular glutathione.
abstract: Glutathione (GSH) is one of the major antioxidants in the brain. GSH is secreted by astrocytes and this extracellular GSH is used by neurones to maintain and increase their intracellular GSH levels. For efficient GSH trafficking between astrocytes and neurones, GSH needs to be maintained in the reduced form. In model systems, GSH trafficking has been shown to be essential for neuroprotection against a variety of stress conditions. Previously we and others have shown that GSH and thiols are unstable in cell culture media and are easily oxidised. In the present study it is shown that nanomolar concentrations of copper (II) ions can cause decay of GSH in cell culture media. Increased free or redox active copper has been implicated in a variety of diseases and degradation of extracellular GSH is a possible mechanism by which it exerts its harmful effects. Rat astrocytes, a human astrocytoma cell line and astrocyte-conditioned media, in the absence of cells, are able to retard this copper-catalysed decay of GSH and maintain GSH in its reduced form. The protective effect of astrocytes appears to be a combination of copper removing and antioxidant mechanisms. The importance of these protective mechanisms is discussed with regards to neurodegenerative diseases.
authors.affiliation: Division of Neurochemistry, Department of Molecular Neuroscience, Institute of Neurology, University College London, London WC1N 3BG, UK. spope@ion.ucl.ac.uk
authors.forename: Simon A S
authors.initials: SA
authors.lastname: Pope
authors.forename: Rosemary
authors.initials: R
authors.lastname: Milton
authors.forename: Simon J R
authors.initials: SJ
authors.lastname: Heales
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001253:Astrocytes / Q000502:physiology*; D001254:Astrocytoma / Q000378:metabolism; D001932:Brain Neoplasms / Q000378:metabolism; D002384:Catalysis; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000378:metabolism*; D017077:Culture Media, Conditioned; D005110:Extracellular Space / Q000378:metabolism*; D005456:Fluorescent Dyes; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D004369:Pentetic Acid / Q000494:pharmacology; D010618:Phenanthrolines; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002614:Chelating Agents; D017077:Culture Media, Conditioned; D005456:Fluorescent Dyes; D010618:Phenanthrolines; C028559:bathocuproine sulfonate; D003300:Copper; D004369:Pentetic Acid; D007770:L-Lactate Dehydrogenase; D005978:Glutathione; D001205:Ascorbic Acid