TY - JOUR
T1 - One- and Two-Electron Oxidations of β-Amyloid25-35 by Carbonate Radical Anion (CO3•-) and Peroxymonocarbonate (HCO4-)
T2 - Role of Sulfur in Radical Reactions and Peptide Aggregation
AU - Francioso, Antonio
AU - Baseggio Conrado, Alessia
AU - Blarzino, Carla
AU - Foppoli, Cesira
AU - Montanari, Elita
AU - Dinarelli, Simone
AU - Giorgi, Alessandra
AU - Mosca, Luciana
AU - Fontana, Mario
N1 - This research was funded by Sapienza Ateneo 2019 Avvio alla Ricerca (“Sapienza” University of Rome) and EMBO grant to A.F.
PY - 2020/2/20
Y1 - 2020/2/20
N2 - 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 Aβ25-35 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 (HCO4-, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•-). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO3•- 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.
AB - 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 Aβ25-35 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 (HCO4-, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•-). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO3•- 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.
KW - Carbonate radical anion
KW - Methionine sulfoxide
KW - Peroxymonocarbonate
KW - Reactive sulfur species
KW - Sulfur centered radical
KW - Sulfur radical cation
KW - β-amyloid
UR - http://www.scopus.com/inward/record.url?scp=85079881852&partnerID=8YFLogxK
U2 - 10.3390/molecules25040961
DO - 10.3390/molecules25040961
M3 - Article
C2 - 32093407
VL - 25
JO - Molecules
JF - Molecules
SN - 1420-3049
IS - 4
M1 - 961
ER -