title: Amyloid beta-peptide spin trapping. I: Peptide enzyme toxicity is related to free radical spin trap reactivity.
abstract: Synthetic beta-amyloid peptides (A betas) demonstrate lot-to-lot variation in toxicity that has not been adequately explained. Studies from our laboratory have shown that A beta toxicity may result from the ability of the peptide to promote oxidation reactions. Both A beta(1-40) and A beta(25-35) inactivate the oxidation-sensitive enzyme glutamine synthetase (GS) and generate electron paramagnetic resonance (EPR)-detectable products upon reaction with the spin trap phenyl-tert-butylnitrone (PBN). We now report that samples of synthetic A beta(1-40) and A beta(25-35) with attenuated toxicity with respect to peptide-induced GS inactivation, produce qualitatively different EPR spectra when the peptides are incubated with PBN. The results suggest an interpretation of conflicting observations regarding the toxicity of synthetic A betas, and that investigators must be careful to assess the reactivity state of A beta being studied.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington 40506, USA.
authors.forename: K
authors.initials: K
authors.lastname: Hensley
authors.forename: M
authors.initials: M
authors.lastname: Aksenova
authors.forename: J M
authors.initials: JM
authors.lastname: Carney
authors.forename: M
authors.initials: M
authors.lastname: Harris
authors.forename: D A
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000596:Amino Acids / Q000032:analysis; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000633:toxicity*; D002851:Chromatography, High Pressure Liquid; D005609:Free Radicals; D010455:Peptides / Q000633:toxicity
chemical_list: D000596:Amino Acids; D016229:Amyloid beta-Peptides; D005609:Free Radicals; D010455:Peptides