AMYLOID BETA-PEPTIDE SPIN-TRAPPING .1. PEPTIDE ENZYME TOXICITY IS RELATED TO FREE-RADICAL SPIN TRAP REACTIVITY

SYNTHETIC beta-amyloid peptides (A beta s) 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(140) 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 beta s, and that investigators must be careful to assess the reactivity state of A beta being studied.