Oxidative modification of glutamine synthetase by amyloid beta peptide.
beta-Amyloid peptide (A beta), the main constituent of senile plaques and diffuse amyloid deposits in Alzheimer's diseased brain, was shown to initiate the development of oxidative stress in neuronal cell cultures. Toxic lots of A beta form free radical species in aqueous solution. It was proposed that A beta-derived free radicals can directly damage cell proteins via oxidative modification. Recently we reported that synthetic A beta can interact with glutamine synthetase (GS) and induce inactivation of this enzyme. In the present study we present the evidence that toxic A beta(25-35) induces the oxidation of pure GS in vitro. It was found that inactivation of GS by A beta, as well as the oxidation of GS by metal-catalyzed oxidation system, is accompanied by an increase of protein carbonyl content. As it was reported previously by our laboratory, radicalization of A beta is not iron or peroxide-dependent. Our present observations consistently show that toxic A beta does not need iron or peroxide to oxidize GS. However, treatment of GS with the peptide, iron and peroxide together significantly stimulates the protein carbonyl formation. Here we report also that A beta(25-35) induces carbonyl formation in BSA. Our results demonstrate that beta-peptide, as well as other free radical generators, induces carbonyl formation when brought into contact with different proteins.
Aksenov
M Y
MY
Department of Pharmacology, University of Kentucky, Lexington 40536, USA. mikeal@uky.campus.mci.net
Aksenova
M V
MV
Carney
J M
JM
Butterfield
D A
DA
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000201:enzymology; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism*; D006861:Hydrogen Peroxide; D007501:Iron; D007700:Kinetics; D009842:Oligopeptides / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010446:Peptide Fragments / Q000494:pharmacology; D012756:Sheep; D013381:Subtilisins / Q000494:pharmacology
D016229:Amyloid beta-Peptides; C045076:Fenton's reagent; D009842:Oligopeptides; D010446:Peptide Fragments; D006861:Hydrogen Peroxide; D007501:Iron; D013381:Subtilisins; D005974:Glutamate-Ammonia Ligase