Free Superoxide is an Intermediate in the Production of H2O2 by Copper(I)‐Aβ Peptide and O2 |
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| Authors: | Dr Karine Reybier Sara Ayala Dr Bruno Alies Dr João V Rodrigues Susana Bustos Rodriguez Dr Giovanni La Penna Dr Fabrice Collin Dr Cláudio M Gomes Dr Christelle Hureau Prof Dr Peter Faller |
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| Institution: | 1. University of Toulouse, UPS;2. UMR 152 PHARMA-DEV, Toulouse cedex 9, France;3. IRD, UMR 152, Toulouse cedex 9, France;4. CNRS, LCC (Laboratoire de Chimie de Coordination), Toulouse Cedex 4, France;5. University of Toulouse, UPS, INPT, Toulouse Cedex 4, France;6. Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras, Portugal;7. Harvard University, Department of Chemistry and Chemical Biology, Cambridge, MA, USA;8. CNR – National Research Council of Italy, ICCOM – Institute for Chemistry of Organo-Metallic Compounds, Firenze, Italy;9. Faculdade de Ciências, Biosystems and Integrative Sciences Institute, Department of Chemistry and Biochemistry, Universidade de Lisboa, Campo Grande, Lisboa, Portugal;10. Institute de Chimie (UMR 7177), Strasbourg, France |
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| 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. |
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| Keywords: | Alzheimer's disease amyloid peptide bioinorganic chemistry copper reactive oxygen species |
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