4-Hydroxynonenal oxidatively modifies histones: Implications for Alzheimer's disease

Jennifer Drake, Robin Petroze, Alessandra Castegna, Qunxing Ding, Jeffrey N. Keller, William R. Markesbery, Mark A. Lovell, D. Allan Butterfield

Research output: Contribution to journalArticle

Abstract

There is increasing evidence of DNA oxidation and altered DNA repair mechanisms in Alzheimer's disease (AD) brain. Histones, which interact with DNA, conceivably could provide a protective shield for DNA against oxidative stress. However, because of their abundant lysine residues, histones may be a target for 4-hydroxynonenal (HNE) modification. In this study, we have shown that HNE binds to histones and that this binding affects the conformation of the histone, measured by electron paramagnetic resonance in conjunction with a protein-specific spin label. The covalent modification to the histone by HNE affects the ability of the histone to bind DNA. Interestingly, acetylated histones appear to be more susceptible to HNE modifications than control histones. Conceivably, altered DNA-histone interactions, subsequent to oxidative modification of histones by the lipid peroxidation product HNE, may contribute to the vulnerability of DNA to oxidation in AD brain.

Original languageEnglish
Pages (from-to)155-158
Number of pages4
JournalNeuroscience Letters
Volume356
Issue number3
DOIs
Publication statusPublished - Feb 19 2004

Keywords

  • Alzheimer's disease
  • DNA oxidation
  • Histone-DNA interactions
  • Protein conformation
  • Spin labeling

ASJC Scopus subject areas

  • Neuroscience(all)

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    Drake, J., Petroze, R., Castegna, A., Ding, Q., Keller, J. N., Markesbery, W. R., Lovell, M. A., & Butterfield, D. A. (2004). 4-Hydroxynonenal oxidatively modifies histones: Implications for Alzheimer's disease. Neuroscience Letters, 356(3), 155-158. https://doi.org/10.1016/j.neulet.2003.11.047