Quantitative proteomic analysis of mitochondria from primary neuron cultures treated with amyloid beta peptide

Mark A. Lovell, Shuling Xiong, William R. Markesbery, Bert C. Lynn

Research output: Contribution to journalArticlepeer-review

51 Scopus citations

Abstract

Increasing evidence supports a role for altered mitochondrial function in the pathogenesis of neuron degeneration in Alzheimer's disease (AD). Although several studies have examined the effect of amyloid beta peptide (Aβ), on activities of individual proteins in primary neuron cultures, there have been no studies of the effects of Aβ on the mitochondrial proteome. Here, we quantitatively measured changes in mitochondrial proteins of primary rat cortical neuron cultures exposed to 25 μM Aβ25-35 for 16 h using isotope coded affinity tag (ICAT) labeling and 2-dimensional liquid chromatography/tandem mass spectrometry (2D-LC/MS/MS) which allows simultaneous identification and quantification of cysteine-containing proteins. The analysis of enriched mitochondrial fractions identified 10 proteins including sodium/potassium-transporting ATPase, cofilin, dihydropyrimidinase, pyruvate kinase and voltage dependent anion channel 1 that were statistically significantly (P < 0.05) altered in Aβ-treated cultures. Elevations of proteins associated with energy production suggest that cells undergoing Aβ-mediated apoptosis increase synthesis of proteins essential for ATP production and efflux in an attempt to maintain metabolic function.

Original languageEnglish
Pages (from-to)113-122
Number of pages10
JournalNeurochemical Research
Volume30
Issue number1
DOIs
StatePublished - Jan 2005

Bibliographical note

Funding Information:
This work was supported by National Institutes of Health grants 5P50-AG05144 and 5P01-AG05119 and by a grant from the Abercrombie Foundation. The authors thank Ms. Paula Thomason for editorial assistance.

Keywords

  • 2D-LC/MS/MS
  • Alzheimer's disease
  • Amyloid beta peptide
  • ICAT

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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