Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes: Implications for Alzheimer's disease

Debra Boyd-Kimball, Alessandra Castegna, Rukhsana Sultana, H. Fai Poon, Robin Petroze, Bert C. Lynn, Jon B. Klein, D. Allan Butterfield

Research output: Contribution to journalArticle

Abstract

Protein oxidation has been implicated in Alzheimer's disease (AD) and can lead to loss of protein function, abnormal protein turnover, interference with cell cycle, imbalance of cellular redox potential, and eventually cell death. Recent proteomics work in our laboratory has identified specifically oxidized proteins in AD brain such as: creatine kinase BB, glutamine synthase, ubiquitin carboxy-terminal hydrolase L-1, dihydropyrimidase-related protein 2, α-enolase, and heat shock cognate 71, indicating that a number of cellular mechanisms are affected including energy metabolism, excitotoxicity and/or synaptic plasticity, protein turnover, and neuronal communication. Synapse loss is known to be an early pathological event in AD, and incubation of synaptosomes with amyloid beta peptide 1-42 (Aβ 1-42) leads to the formation of protein carbonyls. In order to test the involvement of Aβ(1-42) in the oxidation of proteins in AD brain, we utilized two-dimensional gel electrophoresis, immunochemical detection of protein carbonyls, and mass spectrometry to identify proteins from synaptosomes isolated from Mongolian gerbils. Aβ(1-42) treatment leads to oxidatively modified proteins, consistent with the notion that Aβ(1-42)-induced oxidative stress plays an important role in neurodegeneration in AD brain. In this study, we identified β-actin, glial fibrillary acidic protein, and dihydropyrimidinase-related protein-2 as significantly oxidized in synaptosomes treated with Aβ(1-42). Additionally, H+-transporting two-sector ATPase, syntaxin binding protein 1, glutamate dehydrogenase, γ-actin, and elongation factor Tu were identified as increasingly carbonylated. These results are discussed with respect to their potential involvement in the pathogenesis of AD.

Original languageEnglish
Pages (from-to)206-215
Number of pages10
JournalBrain Research
Volume1044
Issue number2
DOIs
Publication statusPublished - May 24 2005

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Synaptosomes
Proteomics
Alzheimer Disease
Proteins
Actins
Brain
Ubiquitin Thiolesterase
BB Form Creatine Kinase
Protein Carbonylation
Peptide Elongation Factor Tu
Qa-SNARE Proteins
Glutamate Dehydrogenase
Neuronal Plasticity
Phosphopyruvate Hydratase
Gerbillinae
Glial Fibrillary Acidic Protein
Electrophoresis, Gel, Two-Dimensional
Glutamine
Synapses
Energy Metabolism

Keywords

  • Alzheimer's disease
  • Amyloid β-peptide (1-42)
  • Amyloid β-peptide (42-1)
  • Oxidative stress
  • Proteomics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Boyd-Kimball, D., Castegna, A., Sultana, R., Poon, H. F., Petroze, R., Lynn, B. C., ... Butterfield, D. A. (2005). Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes: Implications for Alzheimer's disease. Brain Research, 1044(2), 206-215. https://doi.org/10.1016/j.brainres.2005.02.086

Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes : Implications for Alzheimer's disease. / Boyd-Kimball, Debra; Castegna, Alessandra; Sultana, Rukhsana; Poon, H. Fai; Petroze, Robin; Lynn, Bert C.; Klein, Jon B.; Butterfield, D. Allan.

In: Brain Research, Vol. 1044, No. 2, 24.05.2005, p. 206-215.

Research output: Contribution to journalArticle

Boyd-Kimball, D, Castegna, A, Sultana, R, Poon, HF, Petroze, R, Lynn, BC, Klein, JB & Butterfield, DA 2005, 'Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes: Implications for Alzheimer's disease', Brain Research, vol. 1044, no. 2, pp. 206-215. https://doi.org/10.1016/j.brainres.2005.02.086
Boyd-Kimball, Debra ; Castegna, Alessandra ; Sultana, Rukhsana ; Poon, H. Fai ; Petroze, Robin ; Lynn, Bert C. ; Klein, Jon B. ; Butterfield, D. Allan. / Proteomic identification of proteins oxidized by Aβ(1-42) in synaptosomes : Implications for Alzheimer's disease. In: Brain Research. 2005 ; Vol. 1044, No. 2. pp. 206-215.
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