Cited by 62Alzheimer's disease research and treatmentsMetal-Catalyzed Oxygenation MechanismsFree Radicals and Antioxidants

Ascorbate Oxidation by Cu(Amyloid-β) Complexes: Determination of the Intrinsic Rate as a Function of Alterations in the Peptide Sequence Revealing Key Residues for Reactive Oxygen Species Production

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Atrián-Blasco, Elena, del Barrio, Melisa, Faller, Peter, Hureau, Christelle·2018·Analytical Chemistry

Abstract

Along with aggregation of the amyloid-β (Aβ) peptide and subsequent deposit of amyloid plaques, oxidative stress is an important feature in Alzheimer's disease. Cu bound to Aβ is able to produce reactive oxygen species (ROS) by the successive reductions of molecular dioxygen, and the ROS produced contribute to oxidative stress. In vitro, ascorbate consumption parallels ROS production, where ascorbate is the reductant that fuels the reactions. Because the affinity of Cu for Aβ is moderate compared to other biomolecules, the rate of ascorbate consumption is a combination of two contributions. The first one is due to peptide-unbound Cu and the second one to peptide-bound Cu complexes. In the present Article, we aim to determine the amounts of the second contribution in the global ascorbate consumption process. It is defined as the intrinsic rate of ascorbate oxidation, which mathematically corresponds to the rate at an infinite peptide to Cu ratio, i.e., without any contribution from peptide-unbound Cu. We show that, for the wild-type Cu(Aβ) complex, this value equals 10% of the value obtained for peptide-unbound Cu and that this value is strongly dependent on peptide alterations. By examination of the dependence of the intrinsic rate of ascorbate oxidation, followed by UV-vis spectroscopy, for several altered peptides, we determine some of the key residues that influence ROS production.

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Authors
Atrián-Blasco, E., del Barrio, M., Faller, P., & Hureau, C.
Affiliations
  • LCC-CNRS, Université de Toulouse, CNRS, Toulouse, France
  • Centre National de la Recherche Scientifique (FR)
Corresponding author
  • Faller, Peter
  • Hureau, Christelle
Venue
Analytical Chemistry
Published
2018-04-03
Volume
90
Issue
9
Pages
5909-5915
ISSN
  • 0003-2700 (ISSN-L)
  • 1520-6882
OpenAlex
W2795843933
Cited by
62
References
50
Citations by year
2026: 3 · 2025: 8 · 2024: 6 · 2023: 7 · 2022: 10 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 6
FWCI
4.81
Type
journal article
Language
en
Open access
Locations
  • Analytical Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion, other-oa)
Funders
  • Agence Nationale de la Recherche (ANR-13-BSV5-0016)
  • H2020 European Research Council (638712)
  • Universit? de Strasbourg Institut d'?tudes Avanc?es
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Physical Sciences › Chemistry › Inorganic Chemistry › Metal-Catalyzed Oxygenation Mechanisms
  • Physical Sciences › Chemistry › Organic Chemistry › Free Radicals and Antioxidants
Keywords
amyloid-beta, copper complexes, ascorbic acid oxidation, reactive oxygen species, oxidative stress, Alzheimer's disease, key residues
MeSH terms
Amino Acid Sequence, Copper, Organometallic Compounds, Oxidation-Reduction, Amyloid beta-Peptides, Reactive Oxygen Species

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