The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction

Citation
Xd. Huang et al., The A beta peptide of Alzheimer's disease directly produces hydrogen peroxide through metal ion reduction, BIOCHEM, 38(24), 1999, pp. 7609-7616
Citations number
55
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMISTRY
ISSN journal
0006-2960 → ACNP
Volume
38
Issue
24
Year of publication
1999
Pages
7609 - 7616
Database
ISI
SICI code
0006-2960(19990615)38:24<7609:TABPOA>2.0.ZU;2-I
Abstract
Oxidative stress markers characterize the neuropathology both of Alzheimer' s disease and of amyloid-bearing transgenic mice. The neurotoxicity of amyl oid A beta peptides has been linked to peroxide generation in cell cultures by an unknown mechanism. We now show that human A beta directly produces h ydrogen peroxide (H2O2) by a mechanism that involves the reduction of metal ions, Fe(III) or Cu(II), setting up conditions for Fenton-type chemistry. Spectrophotometric experiments establish that the A beta peptide reduces Fe (III) and Cu(II) to Fe(II) and Cu(I), respectively. Spectrochemical techniq ues are used to show that molecular oxygen is then trapped by A beta and re duced to H2O2 in a reaction that is driven by substoichiometric amounts of Fe(II) or Cu(I), In the presence of Cu(II) or Fe(III), A beta produces a po sitive thiobarbituric-reactive substance (TEARS) assay, compatible with the generation of the hydroxyl radical (OH). The amounts of both reduced metal and TEARS reactivity are greatest when generated by A beta-42 much greater than A beta 1-40 > rat A beta 1-40, a chemical relationship that correlate s with the participation of the native peptides in amyloid pathology, These findings indicate that the accumulation of A beta could be a direct source of oxidative stress in Alzheimer's disease.