Impact of N-Truncated Aβ Peptides on Cu- and Cu(Aβ)-Generated ROS: Cu I Matters!

Autor: Esmieu C; CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099 31077, Toulouse Cedex 4, France., Ferrand G; CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099 31077, Toulouse Cedex 4, France.; UPS, INPT, University of Toulouse, 31077, Toulouse Cedex 4, France., Borghesani V; CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099 31077, Toulouse Cedex 4, France.; UPS, INPT, University of Toulouse, 31077, Toulouse Cedex 4, France.; current address: School of Chemistry, University of Birmingham, Edgbaston, B15 2TT, UK., Hureau C; CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099 31077, Toulouse Cedex 4, France.; UPS, INPT, University of Toulouse, 31077, Toulouse Cedex 4, France.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2021 Jan 21; Vol. 27 (5), pp. 1777-1786. Date of Electronic Publication: 2020 Dec 14.
DOI: 10.1002/chem.202003949
Abstrakt: In vitro Cu(Aβ 1-x )-induced ROS production has been extensively studied. Conversely, the ability of N-truncated isoforms of Aβ to alter the Cu-induced ROS production has been overlooked, even though they are main constituents of amyloid plaques found in the human brain. N-Truncated peptides at the positions 4 and 11 (Aβ 4-x and Aβ 11-x ) contain an amino-terminal copper and nickel (ATCUN) binding motif (H 2 N-Xxx-Zzz-His) that confer them different coordination sites and higher affinities for Cu II compared to the Aβ 1-x peptide. It has further been proposed that the role of Aβ 4-x peptide is to quench Cu II toxicity in the brain. However, the role of Cu I coordination has not been investigated to date. In contrast to Cu II , Cu I coordination is expected to be the same for N-truncated and N-intact peptides. Herein, we report in-depth characterizations and ROS production studies of Cu (Cu I and Cu II ) complexes of the Aβ 4-16 and Aβ 11-16 N-truncated peptides. Our findings show that the N-truncated peptides do produce ROS when Cu I is present in the medium, albeit to a lesser extent than the unmodified counterpart. In addition, when used as competitor ligands (i.e., in the presence of Aβ 1-16 ), the N-truncated peptides are not able to fully preclude Cu(Aβ 1-16 )-induced ROS production.
(© 2020 Wiley-VCH GmbH.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje