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Redox Chemistry of Copper–Amyloid‐β: The Generation of Hydroxyl Radical in the Presence of Ascorbate is Linked to Redox‐Potentials and Aggregation State
Author(s) -
Guilloreau Luc,
Combalbert Sarah,
SourniaSaquet Alix,
Mazarguil Honoré,
Faller Peter
Publication year - 2007
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200700111
Subject(s) - redox , chemistry , copper , reactive oxygen species , peptide , cyclic voltammetry , biophysics , amyloid (mycology) , hydroxyl radical , reducing agent , inorganic chemistry , radical , biochemistry , electrochemistry , organic chemistry , electrode , biology
Aggregation of the β‐amyloid peptide (Aβ) to amyloid plaques is a key event in Alzheimer's disease. According to the amyloid‐cascade hypothesis, Aβ aggregates are toxic to neurons through the production of reactive oxygen species (ROS). Copper ions play an important role, because they are able to bind to Aβ and influence its aggregation properties. Moreover, Cu–Aβ is supposed to be directly involved in ROS production. To get a better understanding of these reactions, we measured the production of HO . and the redox potential of Cu–Aβ. The results were compared to other biological copper–peptide complexes in order to get an insight into the biological relevance. Cu–Aβ produced more HO . than the complex of copper with Asp‐Ala‐His‐Lys (Cu–DAHK), but less than with Gly‐His‐Lys (Cu–GHK). Cyclic voltammetry revealed that the order for reduction potential is Cu–GHK>Cu–Aβ>Cu–DAHK, but for the oxidation potential the order is reversed. Thus, easier copper redox cycling correlated to higher HO . production. The copper complex of the form Aβ1–42 showed a HO . production five‐times higher than that of the form Aβ1–40. Time‐dependence and aggregation studies suggest that an aggregation intermediate is responsible for this increased HO . production.