Histidine availability is decisive in ROS-mediated cytotoxicity of copper complexes of Aβ1-16 peptide

The binding of metal ions to Aβ peptide plays an important role in the etiology of AD. Copper coordinates chiefly to His residues and produces reactive oxygen species (ROS) upon redox cycling. ROS builds enormous burden on the normal functioning of neuronal cells and results into deleterious effects...

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Bibliographic Details
Published in:Free radical research 2016-04, Vol.50 (4), p.405-413
Main Authors: Ginotra, Yamini P., Ramteke, Shefali N., Walke, Gulshan R., Rapole, Srikanth, Kulkarni, Prasad P.
Format: Article
Language:English
Subjects:
Alzheimer's disease
Amino Acid Sequence
Amyloid beta-Peptides - chemistry
amyloid β
Ascorbic Acid - pharmacology
Cell Line, Tumor
Coordination Complexes - chemistry
Coordination Complexes - pharmacology
copper
Copper - chemistry
cytotoxicity
Cytotoxins - chemistry
Cytotoxins - pharmacology
Electrochemical Techniques
Gamma Rays
Histidine - chemistry
Humans
Hydrogen Peroxide - chemistry
Hydrolysis
Neurons - chemistry
Neurons - cytology
Neurons - drug effects
Oxidation-Reduction
Peptide Fragments - chemistry
Protein Binding
reactive oxygen species
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Summary:The binding of metal ions to Aβ peptide plays an important role in the etiology of AD. Copper coordinates chiefly to His residues and produces reactive oxygen species (ROS) upon redox cycling. ROS builds enormous burden on the normal functioning of neuronal cells and results into deleterious effects. Recently, two structurally distinct copper binding sites with contrasting redox properties were characterized. Here, we demonstrate for the first time the effect of binding of two equivalents of Cu 2+ on redox properties and cytotoxicity of Aβ peptide. Our electrochemical data and ascorbate consumption assay suggest that in the presence of two equivalents of copper; Aβ peptide has higher propensity of H 2 O 2 generation. The oxidation of Aβ1-16 peptide due to both gamma radiolysis and metal catalyzed oxidation in the presence of two equivalents of copper is inhibited confirming the binding of both equivalents of copper to peptide. The electrochemical and cytotoxicity study shows that negative shift in the reduction potential is reflected as slightly higher cytotoxicity in SH-SY5Y cell lines for Aβ1-16-Cu 2+ (1:2) complex.
ISSN:1071-5762
1029-2470
DOI:10.3109/10715762.2015.1133907