title: Identification of oxidized plasma proteins in Alzheimer's disease.
abstract: The modification of proteins by reactive oxygen species is central to the pathology of Alzheimer's disease (AD). Previously, we have observed specific oxidized proteins in blood plasma of AD subjects [Biochem. Biophys. Res. Commun. 275 (2000) 678]. Plasma from AD subjects and age-matched controls was subjected to two-dimensional gel electrophoresis (2-DE). Oxidized proteins with new carbonyl groups were detected by reaction with 2,4-dinitrophenylhydrazine, followed by Western blotting with anti-DNP antibody. Seven principal oxidized protein spots (isoelectric point=4.7-5.5; molecular mass=45-65 kDa) were observed, with varying levels of oxidation in plasma samples from both AD and non-AD subjects. Matrix-assisted laser desorption mass spectroscopy (MALDI-TOF/MS) revealed that these oxidized proteins were isoforms of fibrinogen gamma-chain precursor protein and of alpha-1-antitrypsin precursor. These proteins exhibited a two- to sixfold greater specific oxidation index in plasma from AD subjects when compared to controls. Both these proteins have been previously implicated in the pathology of the disease. It is possible that oxidized isoforms of these proteins may serve as biomarkers for AD.
authors.affiliation: Molecular Aging Unit, Department of Molecular Biology and Immunology, University of North Texas, Health Science Center, Fort Worth, TX 76107, USA.
authors.forename: Joungil
authors.initials: J
authors.lastname: Choi
authors.forename: Christina A
authors.initials: CA
authors.lastname: Malakowsky
authors.forename: John M
authors.initials: JM
authors.lastname: Talent
authors.forename: Craig C
authors.initials: CC
authors.lastname: Conrad
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gracy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D006801:Humans; D007525:Isoelectric Focusing; D013058:Mass Spectrometry; D010100:Oxygen / Q000097:blood / Q000378:metabolism*; D020033:Protein Isoforms; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D020033:Protein Isoforms; D010100:Oxygen