Redox modulation of chromatin remodeling:: impact on histone acetylation and deacetylation, NF-κB and pro-inflammatory gene expression
Redox modulation of chromatin remodeling:: impact on histone acetylation and deacetylation, NF-κB and pro-inflammatory gene expression
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DOI：
10.1016/j.bcp.2004.05.042
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发表时间：
2004-09-15
影响因子：
5.8
通讯作者：
Kirkham, P
中科院分区：
文献类型：
--
作者：
Rahman, I;Marwick, J;Kirkham, P
活性氧 (ROS)，无论是直接还是通过形成脂质过氧化产物，如 4-羟基-2-壬烯醛、丙烯醛和 F-2-异前列腺素，可能通过应激激酶（JNK、ERK、p38）和氧化还原敏感转录因子（如 NF-kappaB 和 AP-1）的激活和磷酸化在增强炎症方面发挥作用。这增加了调节一系列不同促炎介质的基因的表达。组蛋白乙酰转移酶 (HAT) 对核心组蛋白 N 末端尾部的特定赖氨酸残基进行乙酰化，导致 DNA 解卷并增加转录因子结合的可及性。相比之下，组蛋白脱乙酰酶 (HDAC) 进行的组蛋白脱乙酰作用通过促进 DNA 缠绕来抑制基因转录，从而限制转录因子的使用。氧化应激激活 NF-κB，通过激活共激活分子上的内在 HAT 活性，导致促炎介质的表达。此外，氧化应激还会抑制 HDAC 活性，从而增强炎症基因表达，从而导致慢性炎症反应。氧化应激还可以增加共激活剂 CBP/p300 和 NF-kappaB 的 p65 亚基之间的复合物形成，表明氧化应激在染色质重塑中发挥着进一步的作用。硫醇分子（谷胱甘肽、N-乙酰基-L-半胱氨酸和 N-半胱氨酸）、膳食多酚（姜黄素-二阿魏酰甲烷和白藜芦醇）、支气管扩张剂茶碱和糖皮质激素的抗氧化和/或抗炎作用均已被证明在通过调节 HDAC 活性和随后的炎症基因表达来控制 NF-κB 激活或染色质重塑中发挥作用。肺上皮细胞。因此，氧化应激调节信号转导和染色质重塑，进而影响肺部的促炎症反应。 (C) 2004 Elsevier Inc. 保留所有权利。
Reactive oxygen species (ROS), either directly or via the formation of lipid peroxidation products, such as 4-hydroxy-2-nonenal, acrolein and F-2-isoprostanes, may play a role in enhancing inflammation through the activation and phosphorylation of stress kinases (JNK, ERK, p38) and redox-sensitive transcription factors such as NF-kappaB and AP-1. This increases the expression of genes regulating a battery of distinct pro-inflammatory mediators. Acetylation by histone acetyltransferase (HAT) of specific lysine residues on the N-terminal tail of core histones, results in uncoiling of the DNA and increased accessibility to transcription factor binding. In contrast, histone deacetylation by histone deacetylase (HDAC) represses gene transcription by promoting DNA winding thereby limiting access to transcription factors. Oxidative stress activates NF-kappaB resulting in expression of pro-inflammatory mediators through the activation of intrinsic HAT activity on co-activator molecules. In addition, oxidative stress also inhibits HDAC activity and in doing so enhances inflammatory gene expression which leads to a chronic inflammatory response. Oxidative stress can also increase complex formation between the co-activator CBP/p300 and the p65 subunit of NF-kappaB suggesting a further role of oxidative stress in chromatin remodeling. The antioxidant and/or anti-inflammatory effects of thiol molecules (glutathione, N-acetyl-L-Cysteine and N-acystelyn), dietary polyphenols (curcumin-diferuloylmethane and resveratrol), the bronchodilator theophylline and glucocorticoids have all been shown to play a role in either controlling NF-kappaB activation or chromatin remodeling through modulation of HDAC activity and subsequently inflammatory gene expression in lung epithelial cells. Thus, oxidative stress regulates both signal transduction and chromatin remodeling which in turn impacts on pro-inflammatory responses in the lungs. (C) 2004 Elsevier Inc. All rights reserved.