PMID: 9166739Jun 1, 1997Paper

Oxidatively induced structural alteration of glutamine synthetase assessed by analysis of spin label incorporation kinetics: relevance to Alzheimer's disease

Journal of Neurochemistry
D A ButterfieldJ M Carney

Abstract

The activity of the astrocytic enzyme glutamine synthetase (GS) is decreased in the Alzheimer's disease brain, which may have relevance to mechanisms of chronic excitotoxicity. The molecular perturbation(s) that results in GS inactivation is not known, although oxidative lesioning of the enzyme is one likely cause. To assess structural perturbation induced in GS by metal-catalyzed oxidation, a series of spin-labeling studies were undertaken. Ovine GS was oxidized by exposure to iron/hydrogen peroxide and subsequently labeled with the thiol-specific nitroxide probe MTS [(1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)methanethiosulfonate]. The reaction of MTS with cysteine residues within GS was monitored in real time by electron paramagnetic resonance spectrometry. Structural perturbation of GS, manifested as decreased thiol accessibility, was inferred from an apparent decrease in the rate constant for the second-order reaction of MTS with protein thiols. A subsequent spin-labeling study was undertaken to compare the structural integrity of GS purified and isolated from Alzheimer's disease-afflicted brain (AD-GS) with that of GS isolated from nondemented, age-matched control brain (C-GS). The rate constant for reaction of MTS wi...Continue Reading

Citations

Dec 18, 2001·Journal of Neuroscience Research·S R Robinson
Aug 18, 2006·Neurochemical Research·Vincenzo GiordanoMenotti Calvani
Dec 14, 2007·Molecular BioSystems·Rukhsana Sultana, D Allan Butterfield
Nov 12, 2009·Expert Review of Neurotherapeutics·Stacey FullerMegan Steele
Nov 26, 2011·Antioxidants & Redox Signaling·D Allan ButterfieldRukhsana Sultana
Apr 29, 2016·Biomedical Reports·Wen-Juan HuangWei-Wei Chen
Nov 3, 2016·Antioxidants & Redox Signaling·Erika M PalmieriAlessandra Castegna
May 20, 2019·Journal of Alzheimer's Disease : JAD·Hugo McGurranNicholas T Bott
Nov 30, 2011·Antioxidants & Redox Signaling·Rommy von Bernhardi, Jaime Eugenín
Mar 23, 2018·Journal of Alzheimer's Disease : JAD·D Allan Butterfield, Debra Boyd-Kimball
Sep 19, 2018·Expert Opinion on Therapeutic Targets·Radhika SharmaAnurag Kuhad
Feb 25, 1999·International Journal of Geriatric Psychiatry·R CacabelosB Winblad
Jun 28, 2003·CNS Drugs·D Allan Butterfield, Chava B Pocernich
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May 21, 2011·Neurochemical Research·Yannick VermeirenPeter P De Deyn
Aug 30, 2011·FEBS Letters·Cristian A Lasagna-Reeves, Rakez Kayed
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Nov 14, 1997·Free Radical Research·M Y AksenovD A Butterfield
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