Downregulation of lung mitochondrial prohibitin in COPD

详细信息	查看全文 | 推荐本文 |

• 作者：Nikolaos Soulitzis^a ; Eirini Neofytou^a ; Maria Psarrou^a ; Aristotelis Anagnostis^a ; Nektarios Tavernarakis^b ; Nikolaos Siafakas^a ; Eleni G. Tzortzaki^a ; ^{tzortzaki@med.uoc.gr}
• 关键词：PHB1 ; FEV1 ; Oxidative stress ; Reactive oxygen species ; Smoking
• 刊名：Respiratory Medicine
• 出版年：2012
• 期刊代码：273_09546111
• 类别：med
• 出版时间：July, 2012
• 卷：106
• 期：7
• 页码：954-961
• 文件大小：431 K

摘要

| Figures/TablesFigures/Tables | ReferencesReferences

Summary

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聽卤聽5.8 years, smoking: 84.6聽卤聽33.6 pack-years, FEV₁ (%pred.): 58.7聽卤聽14.6, FEV₁/FVC (%): 63.8聽卤聽9.4], 15 non-COPD smokers [age: 59.0聽卤聽12.1 years, smoking: 52.5聽卤聽20.8 pack-years, FEV₁ (%pred.): 85.5聽卤聽14.2, FEV₁/FVC (%): 78.5聽卤聽4.7] and 10 non-smokers. Quantitative real-time PCR experiments were carried out for PHB1 and PHB2, using 尾-actin as internal control. Non-COPD smokers exhibited lower PHB1 mRNA levels when compared to non-smokers (0.55聽卤聽0.06 vs. 0.90聽卤聽0.06, P聽=聽0.043), while PHB1 expression was even further decreased in COPD patients (0.32聽卤聽0.02), a statistically significant finding vs. both non-COPD smokers (P聽=聽0.040) and non-smokers (P聽<聽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聽卤聽0.13; non-COPD smokers: 0.97聽卤聽0.08; COPD patients: 0.59聽卤聽0.10, P聽=聽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聽=聽0.004, P_protein聽=聽0.014)]. The significant downregulation 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.