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One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation

The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer’s disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological pro...

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Autores principales: Francioso, Antonio, Baseggio Conrado, Alessia, Blarzino, Carla, Foppoli, Cesira, Montanari, Elita, Dinarelli, Simone, Giorgi, Alessandra, Mosca, Luciana, Fontana, Mario
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070857/
https://www.ncbi.nlm.nih.gov/pubmed/32093407
http://dx.doi.org/10.3390/molecules25040961
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author Francioso, Antonio
Baseggio Conrado, Alessia
Blarzino, Carla
Foppoli, Cesira
Montanari, Elita
Dinarelli, Simone
Giorgi, Alessandra
Mosca, Luciana
Fontana, Mario
author_facet Francioso, Antonio
Baseggio Conrado, Alessia
Blarzino, Carla
Foppoli, Cesira
Montanari, Elita
Dinarelli, Simone
Giorgi, Alessandra
Mosca, Luciana
Fontana, Mario
author_sort Francioso, Antonio
collection PubMed
description The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer’s disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aβ most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aβ(25-35) fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO(4)(−), PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO(3)(•−)). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO(3)(•−) causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS(•+)). The formation of this transient reactive intermediate during Aβ oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation.
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spelling pubmed-70708572020-03-19 One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation Francioso, Antonio Baseggio Conrado, Alessia Blarzino, Carla Foppoli, Cesira Montanari, Elita Dinarelli, Simone Giorgi, Alessandra Mosca, Luciana Fontana, Mario Molecules Article The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer’s disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aβ most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aβ(25-35) fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO(4)(−), PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO(3)(•−)). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO(3)(•−) causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS(•+)). The formation of this transient reactive intermediate during Aβ oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation. MDPI 2020-02-20 /pmc/articles/PMC7070857/ /pubmed/32093407 http://dx.doi.org/10.3390/molecules25040961 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Francioso, Antonio
Baseggio Conrado, Alessia
Blarzino, Carla
Foppoli, Cesira
Montanari, Elita
Dinarelli, Simone
Giorgi, Alessandra
Mosca, Luciana
Fontana, Mario
One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation
title One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation
title_full One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation
title_fullStr One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation
title_full_unstemmed One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation
title_short One- and Two-Electron Oxidations of β-Amyloid(25-35) by Carbonate Radical Anion (CO(3)(•−)) and Peroxymonocarbonate (HCO(4)(−)): Role of Sulfur in Radical Reactions and Peptide Aggregation
title_sort one- and two-electron oxidations of β-amyloid(25-35) by carbonate radical anion (co(3)(•−)) and peroxymonocarbonate (hco(4)(−)): role of sulfur in radical reactions and peptide aggregation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7070857/
https://www.ncbi.nlm.nih.gov/pubmed/32093407
http://dx.doi.org/10.3390/molecules25040961
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