Glutamine synthetase-induced enhancement of beta-amyloid peptide A beta (1-40) neurotoxicity accompanied by abrogation of fibril formation and A beta fragmentation.
beta-Amyloid peptide (A beta) is the main constituent in both senile plaques and diffuse deposits in Alzheimer's diseased brains. It was previously shown that synthetic A beta s were able to form free radical species in aqueous solution and cause both oxidative damage to cell proteins and inactivation of key metabolic enzymes. We also previously demonstrated that an interaction of A beta (1-40) with the oxidatively sensitive enzyme glutamine synthetase (GS) resulted in both inactivation of GS and an increase of A beta toxicity to hippocampal cell cultures. In the present study the enhancement of A beta toxicity during interaction with GS was found to be accompanied by abrogation of fibril formation and partial fragmentation of A beta (1-40). HPLC elution profiles demonstrated the production of several peptide fragments. Analysis of the amino acid sequence of the major fragments identified them as the first 15 and the last six amino acids of A beta (1-40). The fragmentation of A beta was inhibited by immunoprecipitation of GS.
Aksenov
M Y
MY
Department of Pharmacology, University of Kentucky, Lexington 40536, USA.
Aksenova
M V
MV
Butterfield
D A
DA
Hensley
K
K
Vigo-Pelfrey
C
C
Carney
J M
JM
D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D005974:Glutamate-Ammonia Ligase / Q000494:pharmacology*; D008854:Microscopy, Electron; D008968:Molecular Conformation; D009498:Neurotoxins / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000494:pharmacology* / Q000502:physiology*; D012756:Sheep
D016229:Amyloid beta-Peptides; D009498:Neurotoxins; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D005974:Glutamate-Ammonia Ligase