Cellular response to cigarette smoke and oxidants: adapting to survive.
Cellular response to cigarette smoke and oxidants: adapting to survive.
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DOI：
10.1513/pats.201001-014aw
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发表时间：
2010-11-01
期刊：
影响因子：
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通讯作者：
Cantin, Andre M
中科院分区：
文献类型：
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作者：
Cantin, Andre M
香烟烟雾的气相和可溶相是导致慢性阻塞性肺疾病（COPD）发病的氧化剂的来源。吸烟的慢性氧化应激诱导粘液分泌并抑制囊性纤维化跨膜传导调节器功能。粘液粘度增加使气道容易受到细菌感染，这是慢性支气管炎的标志。此外，长期暴露于香烟烟雾中的氧化剂的有毒混合物的肺显示内质网应激、未折叠蛋白质反应、改变的神经酰胺代谢和细胞凋亡的迹象。幸运的是，呼吸道已经发展出有效的适应性细胞机制来限制氧化损伤。许多抗氧化酶和谷胱甘肽依赖的解毒系统在健康吸烟者中增加。抗氧化反应的调节很大程度上取决于核因子红细胞2相关因子-2（Nrf 2）途径。然而，COPD患者的Nrf 2反应存在缺陷。新的治疗方法，如2-氰基-3，12-二氧代齐墩果-1，9-二烯-28-酸（CDDO），以纠正缺陷的Nrf 2依赖性细胞反应可能为COPD患者带来希望。
The gaseous and soluble phases of cigarette smoke are sources of oxidants that contribute to the pathogenesis of chronic obstructive pulmonary disease (COPD). Chronic oxidative stress of cigarette smoking induces mucus secretion and inhibits cystic fibrosis transmembrane conductance regulator function. The increased mucus viscosity renders the airways susceptible to bacterial infections, a hallmark of chronic bronchitis. Furthermore, lungs chronically exposed to the toxic mixture of oxidants in cigarette smoke show signs of endoplasmic reticulum stress, unfolded protein response, altered ceramide metabolism, and apoptosis. Fortunately, the respiratory tract has developed effective adaptive cellular mechanisms to limit oxidant damage. Numerous antioxidant enzymes and glutathione-dependent detoxification systems are increased in healthy smokers. The regulation of the antioxidant response is largely dependent on the nuclear factor erythroid 2-related factor-2 (Nrf2) pathway. However, patients with COPD have defective Nrf2 responses. Novel therapies such as 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO) to correct defective Nrf2-dependent cellular response may hold promise for patients with COPD.