TY - JOUR
T1 - 4-Hydroxynonenal oxidatively modifies histones
T2 - Implications for Alzheimer's disease
AU - Drake, Jennifer
AU - Petroze, Robin
AU - Castegna, Alessandra
AU - Ding, Qunxing
AU - Keller, Jeffrey N.
AU - Markesbery, William R.
AU - Lovell, Mark A.
AU - Butterfield, D. Allan
PY - 2004/2/19
Y1 - 2004/2/19
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
KW - DNA oxidation
KW - Histone-DNA interactions
KW - Protein conformation
KW - Spin labeling
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U2 - 10.1016/j.neulet.2003.11.047
DO - 10.1016/j.neulet.2003.11.047
M3 - Article
C2 - 15036618
AN - SCOPUS:0442307849
VL - 356
SP - 155
EP - 158
JO - Neuroscience Letters
JF - Neuroscience Letters
SN - 0304-3940
IS - 3
ER -