title: Increased susceptibility of copper-deficient neuroblastoma cells to oxidative stress-mediated apoptosis.
abstract: Treatment of neuroblastoma cells with the copper chelator triethylene tetramine tetrahydrochloride induced intracellular decrease of copper content paralleled by diminished activity of the enzymes Cu, Zn superoxide dismutase, and cytochrome c oxidase. This effect appears to be specific for copper-enzymes and the treatment affects neither viability nor growth capability of cells. However, molecular markers of apoptosis Bcl-2, p53, and caspase-3 were slightly affected in these cells. When copper-deficient cells were challenged with oxidative stress generated by paraquat or puromycin, they underwent a higher degree of apoptosis with respect to copper-adequate control cells. The mechanism underlying paraquat-triggered apoptosis implies dramatic activation of caspase-3 and induction of the transcription factor p53. These results demonstrate that impairment of copper balance predisposes neuronal cells to apoptosis induced by oxidative stress. Overall findings represent a contribution to the comprehension of the link between copper-imbalance and neurodegeneration, which has recently been repeatedly suggested for the most invalidating pathologies of the central nervous system.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Rome, Italy. luisa.rossi@uniroma2.it
authors.forename: L
authors.initials: L
authors.lastname: Rossi
authors.forename: E
authors.initials: E
authors.lastname: Marchese
authors.forename: M F
authors.initials: MF
authors.lastname: Lombardo
authors.forename: G
authors.initials: G
authors.lastname: Rotilio
authors.forename: M R
authors.initials: MR
authors.lastname: Ciriolo
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D003300:Copper / Q000172:deficiency* / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000187:drug effects; D010269:Paraquat / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011691:Puromycin / Q000494:pharmacology; D013482:Superoxide Dismutase / Q000378:metabolism; D014266:Trientine / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D002614:Chelating Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D011691:Puromycin; D003300:Copper; D013482:Superoxide Dismutase; D003576:Electron Transport Complex IV; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D005978:Glutathione; D010269:Paraquat; D014266:Trientine