title: Free Superoxide is an Intermediate in the Production of H2O2 by Copper(I)-Aβ Peptide and O2.
abstract: Oxidative stress is considered as an important factor and an early event in the etiology of Alzheimer's disease (AD). Cu bound to the peptide amyloid-β (Aβ) is found in AD brains, and Cu-Aβ could contribute to this oxidative stress, as it is able to produce in vitro H2O2 and HO˙ in the presence of oxygen and biological reducing agents such as ascorbate. The mechanism of Cu-Aβ-catalyzed H2O2 production is however not known, although it was proposed that H2O2 is directly formed from O2 via a 2-electron process. Here, we implement an electrochemical setup and use the specificity of superoxide dismutase-1 (SOD1) to show, for the first time, that H2O2 production by Cu-Aβ in the presence of ascorbate occurs mainly via a free O2˙(-) intermediate. This finding radically changes the view on the catalytic mechanism of H2O2 production by Cu-Aβ, and opens the possibility that Cu-Aβ-catalyzed O2˙(-) contributes to oxidative stress in AD, and hence may be of interest.
authors.affiliation: University of Toulouse, UPS; UMR 152 PHARMA-DEV, 118 route de Narbonne, 31062, Toulouse cedex 9, France. karine.reybier-vuattoux@univ-tlse3.fr.|IRD, UMR 152, 31062, Toulouse cedex 9, France. karine.reybier-vuattoux@univ-tlse3.fr.
authors.forename: Karine
authors.initials: K
authors.lastname: Reybier
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France.|University of Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France.
authors.forename: Sara
authors.initials: S
authors.lastname: Ayala
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France.|University of Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Alies
authors.affiliation: Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.|Harvard University, Department of Chemistry and Chemical Biology, Cambridge, MA, USA.
authors.forename: João V
authors.initials: JV
authors.lastname: Rodrigues
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France.|University of Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France.
authors.forename: Susana
authors.initials: S
authors.lastname: Bustos Rodriguez
authors.affiliation: CNR - National Research Council of Italy, ICCOM - Institute for Chemistry of Organo-Metallic Compounds, via Madonna del Piano 10, 50019 Sesto Fiorentino, Firenze, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: La Penna
authors.affiliation: University of Toulouse, UPS; UMR 152 PHARMA-DEV, 118 route de Narbonne, 31062, Toulouse cedex 9, France.|IRD, UMR 152, 31062, Toulouse cedex 9, France.|CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France.|University of Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Collin
authors.affiliation: Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal.|Faculdade de Ciências, Biosystems and Integrative Sciences Institute, Department of Chemistry and Biochemistry, Universidade de Lisboa, Campo Grande, Lisboa, Portugal.
authors.forename: Cláudio M
authors.initials: CM
authors.lastname: Gomes
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France.|University of Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Hureau
authors.affiliation: CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, 31077, Toulouse Cedex 4, France. pfaller@unistra.fr.|University of Toulouse, UPS, INPT, 31077, Toulouse Cedex 4, France. pfaller@unistra.fr.|Institute de Chimie (UMR 7177), 4 rue B. Pascal, 67081, Strasbourg, France. pfaller@unistra.fr.
authors.forename: Peter
authors.initials: P
authors.lastname: Faller
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry*; D003300:Copper / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D010100:Oxygen / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013482:Superoxide Dismutase / Q000737:chemistry; D013481:Superoxides / Q000737:chemistry*
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides; D013481:Superoxides; D003300:Copper; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D010100:Oxygen
keywords: Alzheimer's disease; amyloid peptide; bioinorganic chemistry; copper; reactive oxygen species