Free superoxide is an intermediate in the production of H2O2 by copper(I)-Aβ peptide and O2

Karine Reybier, Sara Ayala, Bruno Alies, João V. Rodrigues, Susana Bustos Rodriguez, Giovanni La Penna, Fabrice Collin, Claudio Emanuel Gomes, Christelle Hureau, Peter Faller

Research output: Contribution to journalArticle

48 Citations (Scopus)

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. Cause of stress: Mechanistic studies reveal that copper-amyloid-β reduces dioxygen and produces predominantly superoxide as an intermediate for H2O2 formation. This finding implies that Cu-Aβ-catalyzed O2.- formation could contribute to oxidative stress in Alzheimer's disease.

Original languageEnglish
Pages (from-to)1085-1089
Number of pages5
JournalAngewandte Chemie-International Edition
Volume55
Issue number3
DOIs
Publication statusPublished - 18 Jan 2016

Keywords

  • Alzheimer's disease
  • amyloid peptide
  • bioinorganic chemistry
  • copper
  • reactive oxygen species

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