Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer.
Cigarette smoke induces distinct histone modifications in lung cells: implications for the pathogenesis of COPD and lung cancer.
复制标题
DOI：
10.1021/pr400998n
复制
发表时间：
2014-02-07
影响因子：
4.4
通讯作者：
Rahman, Irfan
中科院分区：
文献类型：
--
作者：
Sundar, Isaac K.;Nevid, Michael Z.;Friedman, Alan E.;Rahman, Irfan
关键词：
香烟烟雾（CS）介导的氧化应激诱导几个信号级联，包括激酶，这导致染色质修饰（组蛋白乙酰化/脱乙酰化和组蛋白甲基化/去甲基化）。我们以前曾报道，CS诱导染色质重塑的促炎基因启动子，然而，在组蛋白H3和H4中形成的基础位点特异性组蛋白标记CS暴露在体内肺和肺细胞在体外，这可以驱动基因表达或抑制是未知的。我们假设CS暴露在小鼠和人支气管上皮细胞（H292）可以引起位点特异性的翻译后组蛋白修饰（PTM），这可能在CS诱导的慢性肺部疾病的发病机制中发挥重要作用。我们使用自下而上的质谱方法鉴定了一些潜在的新组蛋白标记，包括小鼠肺和H292细胞中组蛋白H3和H4的特定赖氨酸和精氨酸残基的乙酰化，单甲基化和二甲基化。我们发现，CS诱导的组蛋白H3和组蛋白H4在肺细胞中的不同的翻译后组蛋白修饰模式，这可能被认为是有用的生物标志物CS诱导的慢性肺部疾病。组蛋白H3和组蛋白H4可能在吸烟所致慢性肺疾病（如慢性阻塞性肺疾病和肺癌）的表观遗传状态中发挥重要作用。
Cigarette smoke (CS)-mediated oxidative stress induces several signaling cascades, including kinases, which results in chromatin modifications (histone acetylation/deacetylation and histone methylation/demethylation). We have previously reported that CS induces chromatin remodeling in pro-inflammatory gene promoters; however, the underlying site-specific histone marks formed in histones H3 and H4 during CS exposure in lungs in vivo and in lung cells in vitro, which can either drive gene expression or repression are not known. We hypothesize that CS exposure in mouse and human bronchial epithelial cells (H292) can cause site-specific posttranslational histone modifications (PTMs) that may play an important role in the pathogenesis of CS-induced chronic lung diseases. We used a bottom-up mass spectrometry approach to identify some potentially novel histone marks, including acetylation, mono-methylation and di-methylation in specific lysine and arginine residues of histones H3 and H4 in mouse lungs and H292 cells. We found that CS-induced distinct posttranslational histone modification patterns in histone H3 and histone H4 in lung cells, which may be considered as usable biomarkers for CS-induced chronic lung diseases. These identified histone marks (histone H3 and histone H4) may play an important role in epigenetic state during the pathogenesis of smoking-induced chronic lung diseases, such as chronic obstructive pulmonary disease and lung cancer.
登录
查看更多内容
DOI：
10.18632/aging.100023
发表时间：
2009-02-13
期刊：
Aging
影响因子：
--
作者：
Dimauro T;David G
通讯作者：
David G
DOI：
10.1164/rccm.201302-0342oc
发表时间：
2013-09-15
影响因子：
24.7
作者：
Barrero, Carlos A.;Perez-Leal, Oscar;Merali, Salim
通讯作者：
Merali, Salim
影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan
影响因子：
11.4
作者：
Corpet, Armelle;Almouzni, Genevieve
通讯作者：
Almouzni, Genevieve
DOI：
10.1152/ajplung.00426.2009
发表时间：
2010-08-01
影响因子：
4.9
作者：
Chung, Sangwoon;Sundar, Isaac Kirubakaran;Rahman, Irfan
通讯作者：
Rahman, Irfan