Karine Reybier,* Sara Ayala, Bruno Alies, Jo1⁄4o V. Rodrigues, Susana Bustos Rodriguez,
Giovanni La Penna, Fabrice Collin, Clμudio M. Gomes, Christelle Hureau, and Peter Faller*
[*] Dr. K. Reybier, Dr. F. Collin
University of Toulouse, UPS; UMR 152 PHARMA-DEV 118 route de Narbonne, 31062 Toulouse cedex 9 (France) and IRD, UMR 152, 31062 Toulouse cedex 9 (France) E-mail: karine.reybier-vuattoux@univ-tlse3.fr
S. Ayala, Dr. B. Alies, S. Bustos Rodriguez, Dr. F. Collin,
Dr. C. Hureau, Prof. Dr. P. Faller[+++]
CNRS, LCC (Laboratoire de Chimie de Coordination)
205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4 (France) and
University of Toulouse, UPS, INPT 31077 Toulouse Cedex 4 (France) E-mail: pfaller@unistra.fr
Dr. J. V. Rodrigues,[+] Dr. C. M. Gomes[++]
Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras (Portugal)
University of Toulouse, UPS; UMR 152 PHARMA-DEV 118 route de Narbonne, 31062 Toulouse cedex 9 (France) and IRD, UMR 152, 31062 Toulouse cedex 9 (France) E-mail: karine.reybier-vuattoux@univ-tlse3.fr
S. Ayala, Dr. B. Alies, S. Bustos Rodriguez, Dr. F. Collin,
Dr. C. Hureau, Prof. Dr. P. Faller[+++]
CNRS, LCC (Laboratoire de Chimie de Coordination)
205 route de Narbonne, BP 44099, 31077 Toulouse Cedex 4 (France) and
University of Toulouse, UPS, INPT 31077 Toulouse Cedex 4 (France) E-mail: pfaller@unistra.fr
Dr. J. V. Rodrigues,[+] Dr. C. M. Gomes[++]
Instituto Tecnologia Química e Biológica, Universidade Nova de Lisboa, Oeiras (Portugal)
Dr. G. La Penna
CNR – National Research Council of Italy, ICCOM – Institute for Chemistry of Organo-Metallic Compounds
via Madonna del Piano 10, 50019 Sesto Fiorentino, Firenze (Italy)
http://onlinelibrary.wiley.com/doi/10.1002/anie.201508597/abstract
http://onlinelibrary.wiley.com/doi/10.1002/anie.201508597/epdf
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.
CNR – National Research Council of Italy, ICCOM – Institute for Chemistry of Organo-Metallic Compounds
via Madonna del Piano 10, 50019 Sesto Fiorentino, Firenze (Italy)
http://onlinelibrary.wiley.com/doi/10.1002/anie.201508597/abstract
http://onlinelibrary.wiley.com/doi/10.1002/anie.201508597/epdf
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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