Department of Biomedical Sciences, Mercer University School of Medicine, Savannah, GA, USA.
Curr Mol Med. 2012 Aug;12(7):883-98. doi: 10.2174/156652412801318764.
Cigarette smoke (CS) is a risk factor for the development of chronic obstructive pulmonary disease (COPD). Oxidative stress is an immediate result of CS exposure and has the ability to modify cellular proteins. The endoplasmic reticulum (ER) is a compartment where early steps of synthesis and folding of membrane and secretory proteins takes place. Oxidative stress has been shown to interfere with protein folding in the ER and elicits the unfolded protein response (UPR). The UPR is a massive endoplasmic reticulum to the nucleus and the cellular kinase cascades signaling pathway. The UPR triggers a series of intracellular events that aim to help cells overcome the consequences of the stress or eliminate rogue cells by altering expression of genes involved in anti-oxidant defense, cell cycle progression, inflammation, and apoptosis. Recent data demonstrate that CS induces the UPR in vitro and in vivo. The timing of UPR induction in smokers and the mechanism of CS-induced UPR are areas of active investigation. The role of UPR in the protection of smoker's lungs from CS-induced oxidative stress, and its contribution to CS-induced apoptosis and inflammation, is beginning to emerge. This review discusses recent data about UPR in COPD and summarizes findings on UPR that have potential relevance to COPD.
香烟烟雾（CS）是慢性阻塞性肺疾病（COPD）发展的一个风险因素。氧化应激是 CS 暴露的直接结果，并且有能力修饰细胞蛋白。内质网（ER）是一个发生膜和分泌蛋白合成和折叠的早期步骤的隔室。氧化应激已被证明会干扰 ER 中的蛋白折叠，并引发未折叠蛋白反应（UPR）。UPR 是内质网到细胞核和细胞激酶级联信号通路的大规模反应。UPR 触发一系列细胞内事件，旨在帮助细胞克服应激的后果，或通过改变参与抗氧化防御、细胞周期进展、炎症和细胞凋亡的基因的表达来消除流氓细胞。最近的数据表明 CS 在体外和体内诱导 UPR。吸烟者中 UPR 的诱导时间和 CS 诱导 UPR 的机制是正在积极研究的领域。UPR 在保护吸烟者的肺免受 CS 诱导的氧化应激，以及其对 CS 诱导的细胞凋亡和炎症的贡献，正开始显现。这篇综述讨论了关于 COPD 中 UPR 的最新数据，并总结了与 COPD 相关的 UPR 发现。
