title: Copper-dependent toxicity in SH-SY5Y neuroblastoma cells involves mitochondrial damage.
abstract: Treatment of SH-SY5Y human neuroblastoma cells with copper sulphate (50-300microM) in complete medium for 24h caused an increase in the level of the metal both in whole cells and in isolated mitoplasts. Toxic effects of copper resulted in the impairment of the capability of mitochondrial dehydrogenases to reduce a tetrazolium salt, and, to a lesser extent, in the loss of the integrity of the plasma membrane. The mechanism of toxicity involved the production of reactive oxygen species, amplified by the presence of ascorbate. Decreases in the levels of several mitochondrial proteins (subunits of complex I, complex V, and of the pyruvate dehydrogenase complex) were observed. These findings demonstrate that mitochondria are an early and susceptible target of copper-mediated oxidative stress in neuronal cells and support the hypothesis that mitochondrial damage triggers the neurodegenerative processes associated with copper overload in Wilson's disease.
authors.affiliation: Department of Biology, Tor Vergata University of Rome, Via della Ricerca Scientifica, 00133 Rome, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Arciello
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Rotilio
authors.forename: Luisa
authors.initials: L
authors.lastname: Rossi
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003300:Copper / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D024101:Mitochondrial Proteins / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D017382:Reactive Oxygen Species; D003300:Copper; D001205:Ascorbic Acid