Stable Histone Adduction by 4-Oxo-2-nonenal: A Potential Link between Oxidative Stress and Epigenetics

被引:99
作者
Galligan, James J. [1 ,5 ]
Rose, Kristie L. [4 ]
Beavers, William N. [2 ]
Hill, Salisha [4 ]
Tallman, Keri A. [2 ]
Tansey, William P. [6 ]
Marnett, Lawrence J. [1 ,2 ,3 ,5 ]
机构
[1] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Dept Biochem, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Dept Chem, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Dept Pharmacol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Mass Spectrometry Res Ctr, Nashville, TN 37232 USA
[5] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Ctr Mol Toxicol, Nashville, TN 37232 USA
[6] Vanderbilt Univ, Sch Med, AB Hancock Jr Mem Lab Canc Res, Vanderbilt Inst Chem Biol, Nashville, TN 37232 USA
关键词
LIPID-PEROXIDATION; ACETYLATION; PRODUCT; DNA; H4;
D O I
10.1021/ja503604t
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Lipid electrophiles modify cellular targets, altering their function. Here, we describe histones as major targets for modification by 4-oxo-2-nonenal, resulting in a stable Lys modification structurally analogous to other histone Lys acylations. Seven adducts were identified in chromatin isolated from intact cells: four 4-ketoamides to Lys and three Michael adducts to His. A 4-ketoamide adduct residing at H3K27 was identified in stimulated macrophages. Modification of histones H3 and H4 prevented nucleosome assembly.
引用
收藏
页码:11864 / 11866
页数:3
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