Proteomic identification of proteins specifically oxidized by intracerebral injection of amyloid beta-peptide (1-42) into rat brain: implications for Alzheimer's disease.
Protein oxidation has been shown to result in loss of protein function. There is increasing evidence that protein oxidation plays a role in the pathogenesis of Alzheimer's disease (AD). Amyloid beta-peptide (1-42) [Abeta(1-42)] has been implicated as a mediator of oxidative stress in AD. Additionally, Abeta(1-42) has been shown to induce cholinergic dysfunction when injected into rat brain, a finding consistent with cholinergic deficits documented in AD. In this study, we used proteomic techniques to examine the regional in vivo protein oxidation induced by Abeta(1-42) injected into the nucleus basalis magnocellularis (NBM) of rat brain compared with saline-injected control at 7 days post-injection. In the cortex, we identified glutamine synthetase and tubulin beta chain 15/alpha, while, in the NBM, we identified 14-3-3 zeta and chaperonin 60 (HSP60) as significantly oxidized. Extensive oxidation was detected in the hippocampus where we identified 14-3-3 zeta, beta-synuclein, pyruvate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, and phosphoglycerate mutase 1. The results of this study suggest that a single injection of Abeta(1-42) into NBM can have profound effects elsewhere in the brain. The results further suggest that Abeta(1-42)-induced oxidative stress in rat brain mirrors some of those proteins oxidized in AD brain and leads to oxidized proteins, which when inserted into their respective biochemical pathways yields insight into brain dysfunction that can lead to neurodegeneration in AD.
Boyd-Kimball
D
D
Department of Chemistry, Center of Membrane Sciences, University of Kentucky, Lexington, KY 40506-0055, USA.
Sultana
R
R
Poon
H Fai
HF
Lynn
B C
BC
Casamenti
F
F
Pepeu
G
G
Klein
J B
JB
Butterfield
D A
DA
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D047468:Immunoprecipitation / Q000379:methods; D008297:Male; D013058:Mass Spectrometry / Q000379:methods; D010084:Oxidation-Reduction / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D020539:Sequence Analysis, Protein
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011506:Proteins; C075222:amyloid beta-protein (1-42)