title: Expression of a Cu,Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells.
abstract: We have set up a model system for familial amyotrophic lateral sclerosis (FALS) by transfecting human neuroblastoma cell line SH-SY5Y with plasmids directing constitutive expression of either wild-type human Cu,Zn superoxide dismutase (Cu,ZnSOD) or a mutant of this enzyme (G93A) associated with FALS. We have tested mitochondrial function and determined cytosolic Ca2+ concentration in control cells (untransfected) and in cells expressing either wild-type Cu,ZnSOD or G93A. We report that G93A induces a significant loss of mitochondrial membrane potential, an increased sensitivity toward valinomycin and a parallel increase in cytosolic Ca2+ concentration. The above phenomena are not related to total Cu,ZnSOD content and activity in the cell.
authors.affiliation: Department of Biology, University of Rome Tor Vergata, Italy.
authors.forename: M T
authors.initials: MT
authors.lastname: Carrì
authors.forename: A
authors.initials: A
authors.lastname: Ferri
authors.forename: A
authors.initials: A
authors.lastname: Battistoni
authors.forename: L
authors.initials: L
authors.lastname: Famhy
authors.forename: R
authors.initials: R
authors.lastname: Gabbianelli
authors.forename: F
authors.initials: F
authors.lastname: Poccia
authors.forename: G
authors.initials: G
authors.lastname: Rotilio
mesh_terms: D000690:Amyotrophic Lateral Sclerosis / Q000201:enzymology*; D002118:Calcium / Q000378:metabolism*; D003001:Cloning, Molecular; D003600:Cytosol / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000502:physiology*; D009447:Neuroblastoma; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014407:Tumor Cells, Cultured; D014634:Valinomycin / Q000494:pharmacology
chemical_list: D011994:Recombinant Proteins; D014634:Valinomycin; D013482:Superoxide Dismutase; D002118:Calcium