4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer's disease
4-Hydroxynonenal oxidatively modifies histones: implications for Alzheimer's disease
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DOI：
10.1016/j.neulet.2003.11.047
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发表时间：
2004-02-19
影响因子：
2.5
通讯作者：
Butterfield, DA
中科院分区：
文献类型：
--
作者：
Drake, J;Petroze, R;Butterfield, DA
越来越多的证据表明阿尔茨海默病(AD)大脑中的DNA氧化和DNA修复机制发生了变化。可以想象，与DNA相互作用的组蛋白可以为DNA提供抵御氧化应激的保护屏障。然而，由于其丰富的赖氨酸残基，组蛋白可能成为4-羟基壬烯醛(HNE)修饰的目标。在这项研究中，我们已经证明了HNE与组蛋白结合，这种结合影响了组蛋白的构象，通过电子顺磁共振结合蛋白质特异的自旋标记来测量。HNE对组蛋白的共价修饰影响了组蛋白与DNA的结合能力。有趣的是，乙酰化组蛋白似乎比对照组蛋白更容易受到HNE的修饰。可以想象，在组蛋白被脂质过氧化产物HNE氧化修饰后，DNA-组蛋白相互作用的改变可能导致AD脑中DNA对氧化的脆弱性。(C)2003爱思唯尔爱尔兰有限公司。保留所有权利。
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. (C) 2003 Elsevier Ireland Ltd. All rights reserved.