Downregulation of lung mitochondrial prohibitin in COPD
Downregulation of lung mitochondrial prohibitin in COPD
复制标题
DOI：
10.1016/j.rmed.2012.03.019
复制
发表时间：
2012-07-01
影响因子：
4.3
通讯作者：
Tzortzaki, Eleni G.
中科院分区：
文献类型：
--
作者：
Soulitzis, Nikolaos;Neofytou, Eirini;Tzortzaki, Eleni G.
禁止蛋白（PHB1和PHB2）是位于线粒体内膜的多功能蛋白，维持正常的线粒体功能和形态。它们与NADH脱氢酶蛋白复合物相互作用，这是细胞内氧化还原酶活性所必需的。然而，它们在肺上皮中的表达，特别是在吸烟者和与氧化应激增加相关的炎症性肺病（如COPD）患者中的表达尚不清楚。研究了45名男性受试者的肺组织标本：20名COPD患者[年龄：65.7 +/- 5.8岁，吸烟：84.6 +/- 33.6包年，FEV1 (%pred): 58.7 +/- 14.6, FEV1/FVC(%): 63.8 +/- 9.4]， 15名非COPD吸烟者[年龄：59.0 +/- 12.1岁，吸烟：52.5 +/- 20.8包年，FEV (1) (%pred): 85.5 +/- 14.2, FEV1/FVC(%): 78.5 +/- 4.7]和10名非吸烟者。以β -肌动蛋白为内控，对PHB1和PHB2进行实时荧光定量PCR检测。与非吸烟者相比，非COPD吸烟者PHB1 mRNA水平较低（0.55 +/- 0.06比0.90 +/- 0.06,P = 0.043），而COPD患者PHB1表达进一步降低（0.32 +/- 0.02），与非COPD吸烟者（P = 0.040）和非吸烟者（P < 0.001）相比，这一发现具有统计学意义。相比之下，三个研究组的PHB2水平相似。Western blot分析PHB1蛋白验证了qPCR结果（非吸烟者：1.77 +/- 0.13；非COPD吸烟者：0.97 +/- 0.08；COPD患者：0.59 +/- 0.10,P = 0.007）。进一步分析发现，慢性阻塞性肺病患者的PHB1下调不能仅仅归因于吸烟，PHB1表达水平与气道阻塞程度相关[FEV1 (P-mRNA = 0.004, P-protein = 0.014)]。与不吸烟者相比，COPD和非COPD吸烟者中PHB1的显著下调可能反映了线粒体稳定性下降导致的线粒体功能扭曲，尤其是COPD患者的线粒体。(C) 2012 Elsevier Ltd.版权所有。
Prohibitins (PHB1 and PHB2) are versatile proteins located at the inner mitochondrial membrane, maintaining normal mitochondrial function and morphology. They interact with the NADH dehydrogenase protein complex, which is essential for oxidoreductase activity within cells. However, their expression in lung epithelium, especially in smokers and patients with inflammatory lung diseases associated with increased oxidative stress, such as COPD, is unknown. Lung tissue specimens from 45 male subjects were studied: 20 COPD patients [age: 65.7 +/- 5.8 years, smoking: 84.6 +/- 33.6 pack-years, FEV1 (%pred.): 58.7 +/- 14.6, FEV1/FVC (%): 63.8 +/- 9.4], 15 non-COPD smokers [age: 59.0 +/- 12.1 years, smoking: 52.5 +/- 20.8 pack-years, FEV,(1) (%pred.): 85.5 +/- 14.2, FEV1/FVC (%): 78.5 +/- 4.7] and 10 non-smokers. Quantitative real-time PCR experiments were carried out for PHB1 and PHB2, using beta-actin as internal control. Non-COPD smokers exhibited lower PHB1 mRNA levels when compared to non-smokers (0.55 +/- 0.06 vs. 0.90 +/- 0.06, P = 0.043), while PHB1 expression was even further decreased in COPD patients (0.32 +/- 0.02), a statistically significant finding vs. both non-COPD smokers (P = 0.040) and non-smokers (P < 0.001). By contrast, PHB2 levels were similar among the three study groups. Western blot analysis for the PHB1 protein verified the qPCR results (non-smokers: 1.77 +/- 0.13; non-COPD smokers: 0.97 +/- 0.08; COPD patients: 0.59 +/- 0.10, P = 0.007). Further analysis revealed that PHB1 downregulation in COPD patients cannot be attributed solely to smoking, and that PHB1 expression levels are associated with the degree of airway obstruction [FEV1 (P-mRNA = 0.004, P-protein = 0.014)]. The significant down regulation of PHB1 in COPD and non-COPD smokers in comparison to non-smokers possibly reflects a distorted mitochondrial function due to decreased mitochondrial stability, especially in the mitochondria of COPD patients. (C) 2012 Elsevier Ltd. All rights reserved.