title: Histidine availability is decisive in ROS-mediated cytotoxicity of copper complexes of Aβ1-16 peptide.
abstract: 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 H2O2 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.
authors.affiliation: a Bioprospecting Group, Agharkar Research Institute , Pune , Maharashtra , India ;
authors.forename: Yamini P
authors.initials: YP
authors.lastname: Ginotra
authors.affiliation: a Bioprospecting Group, Agharkar Research Institute , Pune , Maharashtra , India ;
authors.forename: Shefali N
authors.initials: SN
authors.lastname: Ramteke
authors.affiliation: a Bioprospecting Group, Agharkar Research Institute , Pune , Maharashtra , India ;
authors.forename: Gulshan R
authors.initials: GR
authors.lastname: Walke
authors.affiliation: b Proteomics Laboratory , National Centre for Cell Science, University of Pune Campus , Pune , Maharashtra , India.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Rapole
authors.affiliation: a Bioprospecting Group, Agharkar Research Institute , Pune , Maharashtra , India ;
authors.forename: Prasad P
authors.initials: PP
authors.lastname: Kulkarni
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D001205:Ascorbic Acid / Q000494:pharmacology; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D003603:Cytotoxins / Q000737:chemistry / Q000494:pharmacology*; D055664:Electrochemical Techniques; D005720:Gamma Rays; D006639:Histidine / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry*; D006868:Hydrolysis; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D010084:Oxidation-Reduction; D010446:Peptide Fragments / Q000737:chemistry*; D011485:Protein Binding
chemical_list: D016229:Amyloid beta-Peptides; D056831:Coordination Complexes; D003603:Cytotoxins; D010446:Peptide Fragments; C433241:amyloid beta-protein (1-16); D006639:Histidine; D003300:Copper; D006861:Hydrogen Peroxide; D001205:Ascorbic Acid
keywords: Alzheimer’s disease; amyloid β; copper; cytotoxicity; reactive oxygen species