title: Redox proteomics identification of oxidized proteins in Alzheimer's disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in AD.
abstract: Alzheimer's disease (AD) is characterized by the presence of neurofibrillary tangles, senile plaques and loss of synapses. There is accumulating evidence that oxidative stress plays an important role in AD pathophysiology. Previous redox proteomics studies from our laboratory on AD inferior parietal lobule led to the identification of oxidatively modified proteins that were consistent with biochemical or pathological alterations in AD. The present study was focused on the identification of specific targets of protein oxidation in AD and control hippocampus and cerebellum using a redox proteomics approach. In AD hippocampus, peptidyl prolyl cis-trans isomerase, phosphoglycerate mutase 1, ubiquitin carboxyl terminal hydrolase 1, dihydropyrimidinase related protein-2 (DRP-2), carbonic anhydrase II, triose phosphate isomerase, alpha-enolase, and gamma-SNAP were identified as significantly oxidized protein with reduced enzyme activities relative to control hippocampus. In addition, no significant excessively oxidized protein spots were identified in cerebellum compared to control, consistent with the lack of pathology in this brain region in AD. The identification of oxidatively modified proteins in AD hippocampus was verified by immunochemical means. The identification of common oxidized proteins in different brain regions of AD brain suggests a potential role for these oxidized proteins and thereby oxidative stress in the pathogenesis of Alzheimer's disease.
authors.affiliation: Department of Chemistry, University of Kentucky, Lexington, KY 40506, USA.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Sultana
authors.forename: Debra
authors.initials: D
authors.lastname: Boyd-Kimball
authors.forename: H Fai
authors.initials: HF
authors.lastname: Poon
authors.forename: Jian
authors.initials: J
authors.lastname: Cai
authors.forename: William M
authors.initials: WM
authors.lastname: Pierce
authors.forename: Jon B
authors.initials: JB
authors.lastname: Klein
authors.forename: Michael
authors.initials: M
authors.lastname: Merchant
authors.forename: William R
authors.initials: WR
authors.lastname: Markesbery
authors.forename: D Allan
authors.initials: DA
authors.lastname: Butterfield
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D002531:Cerebellum / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D006834:Hydrazines; D047468:Immunoprecipitation; D008297:Male; D013058:Mass Spectrometry; D016555:Matched-Pair Analysis; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011506:Proteins / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D014357:Trypsin
chemical_list: D006834:Hydrazines; D011506:Proteins; C446799:dinitrophenylhydrazine; D014357:Trypsin