title: Cu(II) potentiation of alzheimer abeta neurotoxicity. Correlation with cell-free hydrogen peroxide production and metal reduction.
abstract: Oxidative stress markers as well as high concentrations of copper are found in the vicinity of Abeta amyloid deposits in Alzheimer's disease. The neurotoxicity of Abeta in cell culture has been linked to H(2)O(2) generation by an unknown mechanism. We now report that Cu(II) markedly potentiates the neurotoxicity exhibited by Abeta in cell culture. The potentiation of toxicity is greatest for Abeta1-42 > Abeta1-40 >> mouse/rat Abeta1-40, corresponding to their relative capacities to reduce Cu(II) to Cu(I), form H(2)O(2) in cell-free assays and to exhibit amyloid pathology. The copper complex of Abeta1-42 has a highly positive formal reduction potential ( approximately +500-550 mV versus Ag/AgCl) characteristic of strongly reducing cuproproteins. These findings suggest that certain redox active metal ions may be important in exacerbating and perhaps facilitating Abeta-mediated oxidative damage in Alzheimer's disease.
authors.affiliation: Laboratory for Oxidation Biology, Genetics and Aging Unit, and Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
authors.forename: X
authors.initials: X
authors.lastname: Huang
authors.forename: M P
authors.initials: MP
authors.lastname: Cuajungco
authors.forename: C S
authors.initials: CS
authors.lastname: Atwood
authors.forename: M A
authors.initials: MA
authors.lastname: Hartshorn
authors.forename: J D
authors.initials: JD
authors.lastname: Tyndall
authors.forename: G R
authors.initials: GR
authors.lastname: Hanson
authors.forename: K C
authors.initials: KC
authors.lastname: Stokes
authors.forename: M
authors.initials: M
authors.lastname: Leopold
authors.forename: G
authors.initials: G
authors.lastname: Multhaup
authors.forename: L E
authors.initials: LE
authors.lastname: Goldstein
authors.forename: R C
authors.initials: RC
authors.lastname: Scarpa
authors.forename: A J
authors.initials: AJ
authors.lastname: Saunders
authors.forename: J
authors.initials: J
authors.lastname: Lim
authors.forename: R D
authors.initials: RD
authors.lastname: Moir
authors.forename: C
authors.initials: C
authors.lastname: Glabe
authors.forename: E F
authors.initials: EF
authors.lastname: Bowden
authors.forename: C L
authors.initials: CL
authors.lastname: Masters
authors.forename: D P
authors.initials: DP
authors.lastname: Fairlie
authors.forename: R E
authors.initials: RE
authors.lastname: Tanzi
authors.forename: A I
authors.initials: AI
authors.lastname: Bush
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002478:Cells, Cultured; D003198:Computer Simulation; D003300:Copper / Q000378:metabolism / Q000494:pharmacology*; D004578:Electron Spin Resonance Spectroscopy; D006861:Hydrogen Peroxide / Q000378:metabolism*; D010084:Oxidation-Reduction; D051381:Rats
chemical_list: D016229:Amyloid beta-Peptides; D003300:Copper; D006861:Hydrogen Peroxide