Protein oxidation in the brain in Alzheimer's disease

M. Y. Aksenov, M. V. Aksenova, D. A. Butterfield, J. W. Geddes, W. R. Markesbery

Research output: Contribution to journalArticlepeer-review

452 Scopus citations

Abstract

In this study we used immunohistochemistry and two-dimensional fingerprinting of oxidatively modified proteins (two-dimensional Oxyblot) together to investigate protein carbonyl formation in the Alzheimer's disease brain. Increased protein oxidation was detected in sections from the hippocampus and parahippocampal gyrus, superior and middle temporal gyri of six Alzheimer's disease and six age-matched control human subjects, but not in the cerebellum. In two brain regions severely affected by Alzheimer's disease pathology, prominent protein carbonyl immunoreactivity was localized in the cytoplasm of neurons without visual pathomorphological changes and degenerating neurons, suggesting that intracellular proteins might be significantly affected by oxidative modifications. Following two-dimensional electrophoresis the positions of some individual proteins were identified using specific antibodies, and immunoblot analysis for protein carbonyls was performed. These studies demonstrated the presence of protein carbonyl immunoreactivity in β-tubulin, β-actin and creatine kinase BB in Alzheimer's disease and control brain extracts. Protein carbonyls were undetectable in spots matching glial fibrillary acidic protein and tau isoforms. Specific protein carbonyl levels in β-actin and creatine kinase BB were significantly higher in Alzheimer's disease than in control brain extract. β-Tubulin did not demonstrate a significant increase in specific protein carbonyl content in Alzheimer's disease brains. We suggest that oxidative stress-induced injury may involve the selective modification of different intracellular proteins, including key enzymes and structural proteins, which precedes and may lead to the neurofibrillary degeneration of neurons in the Alzheimer's disease brain.

Original languageEnglish
Pages (from-to)373-383
Number of pages11
JournalNeuroscience
Volume103
Issue number2
DOIs
StatePublished - Mar 14 2001

Bibliographical note

Funding Information:
This work was supported by NIH grants 5P01 AG05119, 5P50 AG05144, and grants from the Abercrombie Foundation and the Kleberg Foundation. The authors thank Dianna Tudor and Ela Patel for technical assistance, Jane Meara and Paula Thomason for assistance in manuscript preparation, and Cecil Runyons for subject demographic data. The authors also thank Elan Pharmaceutical for the gift of antibodies.

Keywords

  • 2D electrophoresis
  • 2D western blotting
  • Alzheimer's disease
  • Immunohistochemistry
  • Protein carbonyls
  • Protein oxidation

ASJC Scopus subject areas

  • General Neuroscience

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