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Electrochemical and Conformational Consequences of Copper (Cu I and Cu II ) Binding to β‐Amyloid(1–40)
Author(s) -
Brzyska Maria,
Trzesniewska Katarzyna,
Wieckowska Agnieszka,
Szczepankiewicz Andrzej,
Elbaum Danek
Publication year - 2009
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.200800732
Subject(s) - copper , redox , chemistry , electrochemistry , cyclic voltammetry , metal , conformational change , peptide , amyloid beta , crystallography , thioflavin , biophysics , inorganic chemistry , stereochemistry , alzheimer's disease , biochemistry , electrode , organic chemistry , biology , medicine , disease , pathology
Abstract Copper‐induced structural rearrangements of Aβ40 structure and its redox properties are described in this study. Electrochemical and fluorescent methods are used to characterise the behaviour of Aβ–Cu species. The data suggest that time‐dependent folding of Aβ–Cu species may cause changes in the redox potentials.Extracellular deposits of β‐amyloid (Aβ) into senile plaques are the major features observed in brains of Alzheimer's disease (AD) patients. A high concentration of copper has been associated with insoluble amyloid plaques. It is known that Aβ(1–40) can bind copper with high affinity, but electrochemical properties of Aβ(1–40)–Cu complexes are not well‐characterised. In this study we demonstrate that complexation of copper (both as Cu I and Cu II ) by Aβ(1–40) reduces the metal electrochemical activity. Formation of copper‐Aβ(1–40) complexes is associated with alteration of the redox potential. The data reveal significant redox activity of fresh Aβ–copper solutions. However, copper‐induced structural rearrangements of the peptide, documented by CD, correspond with time‐dependent changes of formal reduction potentials (E 0′ ) of the complex. Fluorescent and electrochemical (cyclic voltammetry and differential pulse voltammetry) techniques suggest that reduction of the redox activity by Aβ–Cu complexes could be attributed to conformational changes that diminished copper accessibility to the external environment. According to our evidence, conformational rearrangements, induced by copper binding to amyloid, elongate the time necessary to attain the same β‐sheet content as for the metal‐free peptide. Although the redox activity of Aβ–Cu complexes diminishes in a time‐dependent manner, they are not completely devoid of toxicity as they destabilize red blood cells osmotic fragility, even after prolonged incubation.