Glutathione S-transferases and their implications in the lung diseases asthma and chronic obstructive pulmonary disease: Early life susceptibility?
Glutathione S-transferases and their implications in the lung diseases asthma and chronic obstructive pulmonary disease: Early life susceptibility?
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DOI：
10.1016/j.redox.2021.101995
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发表时间：
2021-07
期刊：
影响因子：
11.4
通讯作者：
Reynaert NL
中科院分区：
文献类型：
--
作者：
van de Wetering C;Elko E;Berg M;Schiffers CHJ;Stylianidis V;van den Berge M;Nawijn MC;Wouters EFM;Janssen-Heininger YMW;Reynaert NL
我们的肺部每天都暴露在空气污染物、颗粒物、病原体以及肺部过敏原和刺激物中。接触这些物质会导致炎症反应，并可能诱导内源性氧化剂的产生，这可能会导致慢性炎症、组织损伤和重塑。值得注意的是，哮喘和慢性阻塞性肺疾病(COPD)的发展与上述刺激物有关。一些吸入的外来化合物迅速被I相和II相酶系统吸收和处理，这些酶系统在外源物质的解毒过程中起着关键作用，包括谷胱甘肽结合酶谷胱甘肽S转移酶(GSTs)。GSTs，特别是改变其活性的GSTs的遗传变异，已被发现与这些肺部疾病的易感性和进展有关。除了它们在二期代谢中的作用外，有证据表明GST也是正常肺生长的重要介质。因此，GST在成人肺部疾病发展中的作用可能已经开始于子宫，并持续到婴儿期、儿童期和成年。GSTs还可以清除氧化剂，并通过蛋白质-蛋白质相互作用影响信号通路。此外，GSTs还调节蛋白质可逆的氧化后翻译后修饰，即蛋白质S谷胱甘肽基化。因此，GST显示了一系列影响哮喘和COPD发病机制的功能。在这篇综述中，我们将提供每一类哺乳动物胞浆GST的特定功能的概述。随后对它们在健康受试者肺中的表达情况以及在哮喘患者和COPD患者的(上皮细胞)中描述的变化进行了全面的分析。特别强调的是，除解毒作用外，GST的调节特性以及它们在一生中对(不)健康的肺的贡献的新证据。通过提供更全面的了解，量身定制的治疗策略可以设计成影响特定GST的特定功能。
Our lungs are exposed daily to airborne pollutants, particulate matter, pathogens as well as lung allergens and irritants. Exposure to these substances can lead to inflammatory responses and may induce endogenous oxidant production, which can cause chronic inflammation, tissue damage and remodeling. Notably, the development of asthma and Chronic Obstructive Pulmonary Disease (COPD) is linked to the aforementioned irritants. Some inhaled foreign chemical compounds are rapidly absorbed and processed by phase I and II enzyme systems critical in the detoxification of xenobiotics including the glutathione-conjugating enzymes Glutathione S-transferases (GSTs). GSTs, and in particular genetic variants of GSTs that alter their activities, have been found to be implicated in the susceptibility to and progression of these lung diseases. Beyond their roles in phase II metabolism, evidence suggests that GSTs are also important mediators of normal lung growth. Therefore, the contribution of GSTs to the development of lung diseases in adults may already start in utero, and continues through infancy, childhood, and adult life. GSTs are also known to scavenge oxidants and affect signaling pathways by protein-protein interaction. Moreover, GSTs regulate reversible oxidative post-translational modifications of proteins, known as protein S-glutathionylation. Therefore, GSTs display an array of functions that impact the pathogenesis of asthma and COPD. In this review we will provide an overview of the specific functions of each class of mammalian cytosolic GSTs. This is followed by a comprehensive analysis of their expression profiles in the lung in healthy subjects, as well as alterations that have been described in (epithelial cells of) asthmatics and COPD patients. Particular emphasis is placed on the emerging evidence of the regulatory properties of GSTs beyond detoxification and their contribution to (un)healthy lungs throughout life. By providing a more thorough understanding, tailored therapeutic strategies can be designed to affect specific functions of particular GSTs.
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影响因子：
14.2
作者：
Alexis, Neil E.;Zhou, Haibo;Peden, David B.
通讯作者：
Peden, David B.
DOI：
10.3390/molecules20010185
发表时间：
2014-12-24
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Aggarwal BB;Deb L;Prasad S
通讯作者：
Prasad S
DOI：
10.1111/j.1349-7006.2000.tb00946.x
发表时间：
2000-03
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
de Bruin WC;Wagenmans MJ;Peters WH
通讯作者：
Peters WH
影响因子：
4.8
作者：
Board, PG;Coggan, M;Pandit, J
通讯作者：
Pandit, J
影响因子：
6.2
作者：
Allocati N;Masulli M;Di Ilio C;Federici L
通讯作者：
Federici L