Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration
Oxidative stress reduces histone deacetylase 2 activity and enhances IL-8 gene expression: role of tyrosine nitration
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DOI：
10.1016/j.bbrc.2004.01.046
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发表时间：
2004-02-27
影响因子：
3.1
通讯作者：
Adcock, IM
中科院分区：
文献类型：
--
作者：
Ito, K;Hanazawa, T;Adcock, IM
氧化应激是慢性炎症性疾病的一个特征。活性氧中间体过氧化氢（H2O2）是调控基因表达的重要信号分子。我们已经证明H2O2显著增强BEAS-2B细胞的细胞因子产生，在4小时时效果最大。这不是由于NF-kappaB激活增强，而是通过降低组蛋白去乙酰化酶（HDAC）2的活性。这导致特定组蛋白残基乙酰化后炎症基因表达增加。HDAC2活性降低与酪氨酸硝化状态有关。过氧亚硝酸盐和过氧亚硝酸盐生成物SIN-1也能通过酪氨酸硝化降低HDAC2活性。我们的数据表明，氧化应激通过HDAC2硝化作用降低HDAC2活性，从而导致炎症恶化。这种新的炎症机制可能在增加炎症性疾病的严重程度和慢性性方面具有重要意义。(C) 2004爱思唯尔公司版权所有。
Oxidative stress is a characteristic of chronic inflammatory diseases. The reactive oxygen intermediate hydrogen peroxide (H2O2) is an important signaling molecule that modulates gene expression. We have demonstrated that H2O2 significantly enhanced cytokine production in BEAS-2B cells, with a maximal effect at 4 h. This did not result from enhanced NF-kappaB activation, but through decreased activity of histone deacetylase (HDAC)2. This results in increased inflammatory gene expression following acetylation of specific histone residues. Decreased HDAC2 activity was associated with tyrosine nitration status. Peroxynitrite and SIN-1, a peroxynitrite generator, were also able to reduce HDAC2 activity via tyrosine nitration. Our data suggest that oxidative stress contributes to worsening inflammation via reduction of HDAC2 activity through HDAC2 nitration. This novel mechanism of inflammation may be important in increasing the severity and chronicity of inflammatory diseases. (C) 2004 Elsevier Inc. All rights reserved.