Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes.
Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes.
复制标题
牛磺酸通过开启线粒体 NADH 脱氢酶基因改善颗粒物诱发的肺气肿
DOI：
10.1073/pnas.1712465114
复制
发表时间：
2017-11-07
影响因子：
11.1
通讯作者：
Chen R
中科院分区：
文献类型：
--
作者：
Li X;Yang H;Sun H;Lu R;Zhang C;Gao N;Meng Q;Wu S;Wang S;Aschner M;Wu J;Tang B;Gu A;Kay SA;Chen R
暴露于高水平的颗粒物（PM）对人类健康构成重大威胁。香烟烟雾是导致慢性阻塞性肺疾病（COPD）的最常见刺激物；然而，至少四分之一的COPD患者不吸烟，他们的疾病在很大程度上归因于空气污染。中国污染事件的发生引发了一个紧迫的问题，即PM如何导致COPD的发病机制。在本文中，我们表明线粒体NADH脱氢酶基因表达水平的失调在空气污染暴露期间COPD的加重中起关键作用，在哺乳动物细胞和动物中，牛磺酸和3 - 甲基腺嘌呤（3 - MA）处理可以挽救这种情况。
慢性阻塞性肺疾病（COPD）与颗粒物（PM）暴露有关。通过转录组分析，我们证明柴油尾气颗粒（颗粒物排放的主要来源之一）下调位于线粒体复合物I和V的基因，并在小鼠模型中诱发实验性COPD。1 - 硝基芘被确定为PM诱导的COPD的主要毒性成分。在小组研究中，发现COPD患者由于炎症反应增强，比肺功能正常的个体更容易受到PM的影响。从机制上讲，人支气管上皮细胞暴露于PM会导致CCAAT /增强子结合蛋白α（C / EBPα）下降，这引发了NADH脱氢酶基因的异常表达，并最终导致自噬增强。自噬率较低的ATG7缺陷小鼠免受PM诱导的实验性COPD的影响。通过代谢组学分析，我们进一步确定牛磺酸和3 - 甲基腺嘌呤治疗完全恢复了线粒体基因表达水平，从而改善了PM诱导的肺气肿。我们的研究表明针对PM诱导的COPD中C / EBPα/线粒体/自噬轴的一种潜在治疗干预措施。
Exposure to high levels of particulate matter (PM) poses a major threat to human health. Cigarette smoke is the most common irritant that causes chronic obstructive pulmonary disease (COPD); however, at least one-fourth of patients with COPD are nonsmokers, and their disease is largely attributed to air pollution. The occurrence of pollution episodes in China has raised an emergent question of how PM leads to the pathogenesis of COPD. In this paper, we show that deregulation of mitochondrial NADH dehydrogenase gene expression levels plays a key role in the aggravation of COPD during air pollutant exposure, which can be rescued by taurine and 3-MA treatments in both mammalian cells and animals. Chronic obstructive pulmonary disease (COPD) has been linked to particulate matter (PM) exposure. Using transcriptomic analysis, we demonstrate that diesel exhaust particles, one of the major sources of particulate emission, down-regulated genes located in mitochondrial complexes I and V and induced experimental COPD in a mouse model. 1-Nitropyrene was identified as a major toxic component of PM-induced COPD. In the panel study, COPD patients were found to be more susceptible to PM than individuals with normal lung function due to an increased inflammatory response. Mechanistically, exposure to PM in human bronchial epithelial cells led to a decline in CCAAT/enhancer-binding protein alpha (C/EBPα), which triggered aberrant expression of NADH dehydrogenase genes and ultimately led to enhanced autophagy. ATG7-deficient mice, which have lower autophagy rates, were protected from PM-induced experimental COPD. Using metabolomics analysis, we further established that treatment with taurine and 3-methyladenine completely restored mitochondrial gene expression levels, thereby ameliorating the PM-induced emphysema. Our studies suggest a potential therapeutic intervention for the C/EBPα/mitochondria/autophagy axis in PM-induced COPD.
登录
查看更多内容
影响因子：
82.9
作者：
Cloonan SM;Glass K;Laucho-Contreras ME;Bhashyam AR;Cervo M;Pabón MA;Konrad C;Polverino F;Siempos II;Perez E;Mizumura K;Ghosh MC;Parameswaran H;Williams NC;Rooney KT;Chen ZH;Goldklang MP;Yuan GC;Moore SC;Demeo DL;Rouault TA;D'Armiento JM;Schon EA;Manfredi G;Quackenbush J;Mahmood A;Silverman EK;Owen CA;Choi AM
通讯作者：
Choi AM
影响因子：
10.4
作者：
Burnett RT;Pope CA 3rd;Ezzati M;Olives C;Lim SS;Mehta S;Shin HH;Singh G;Hubbell B;Brauer M;Anderson HR;Smith KR;Balmes JR;Bruce NG;Kan H;Laden F;Prüss-Ustün A;Turner MC;Gapstur SM;Diver WR;Cohen A
通讯作者：
Cohen A
DOI：
10.1152/ajplung.00219.2012
发表时间：
2012-11-01
影响因子：
4.9
作者：
Agarwal, Amit R.;Zhao, Liqin;Cadenas, Enrique
通讯作者：
Cadenas, Enrique
呼出气冷凝物和尿液中的丙二醛作为空气污染引起的氧化应激的生物标志物
DOI：
10.1038/jes.2012.127
发表时间：
2013-05
影响因子：
4.5
作者：
通讯作者：
--
影响因子：
168.9
作者：
Lozano, Rafael;Naghavi, Mohsen;Murray, Christopher J. L.
通讯作者：
Murray, Christopher J. L.