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

doi:10.1016/j.neulet.2003.11.047

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

IRCCS Giovanni Paolo II

Research output: Contribution to journal › Article

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 language	English
Pages (from-to)	155-158
Number of pages	4
Journal	Neuroscience Letters
Volume	356
Issue number	3
DOIs	https://doi.org/10.1016/j.neulet.2003.11.047
Publication status	Published - 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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10.1016/j.neulet.2003.11.047

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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

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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.",

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author = "Jennifer Drake and Robin Petroze and Alessandra Castegna and Qunxing Ding and Keller, {Jeffrey N.} and Markesbery, {William R.} and Lovell, {Mark A.} and Butterfield, {D. Allan}",

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AU - Drake, Jennifer

AU - Petroze, Robin

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AU - Ding, Qunxing

AU - Keller, Jeffrey N.

AU - Markesbery, William R.

AU - Lovell, Mark A.

AU - Butterfield, D. Allan

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N2 - 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.

AB - 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.

KW - Alzheimer's disease

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KW - Histone-DNA interactions

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