The response of neurones and glial cells to elevated copper.
Defective copper excretion in Wilson's disease can result in increased neurological copper concentrations. This is thought to occur following exposure to increased circulating copper released from necrotic hepatocytes in a saturated liver. BU17 human glioma cells and SH-SY5Y human neuroblastoma cells were exposed to media supplemented with copper in the range 0-250 microM for periods up to 48 h to investigate this hypothesis. Copper uptake, cell growth, intracellular radical generation, and oxidative stress were measured in copper exposed cells. No increase in copper uptake or inhibition of cell growth could be measured in either cell type at any time point or copper concentration investigated. However, significant increases in radical generation (p < 0.001) could be measured in both BU17 and SH-SY5Y cells. A decreased ability to cope when the cells were exposed to additional pro-oxidants suggested that the cells were under oxidative stress with significant reductions in cell viability following exposure to both copper and ascorbic acid. These data suggest that copper sequestration does not occur in neuronal cells exposed to elevated extracellular copper concentrations.
Watt
N T
NT
School of Biochemistry and Molecular Biology, University of Leeds, Leeds, UK. n.t.watt@leeds.ac.uk
Hooper
N M
NM
D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects* / Q000502:physiology; D003300:Copper / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005609:Free Radicals / Q000378:metabolism*; D006527:Hepatolenticular Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000975:Antioxidants; D005609:Free Radicals; D003300:Copper; D001205:Ascorbic Acid