期刊
RESPIROLOGY
卷 19, 期 8, 页码 1183-1190出版社
WILEY
DOI: 10.1111/resp.12378
关键词
8-oxo-7; 8-dihydro-2 '-deoxyguanosine; chronic obstructive pulmonary disease; human 8-oxoguanine DNA glycosylase; lung tissue; peripheral blood mononuclear cells
资金
- National Natural Science Foundation of China [81070036, 81370145, 81070021, 8130056]
- National Support Program for the Twelfth Five-year Plan [2012BAI05B01]
- Health Public Service Sectors Research Special [201002008]
- Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT1131]
Background and objectiveOxidative stress has long been recognized to play a role in chronic obstructive pulmonary disease (COPD); however, approaches for assessing oxidative stress are lacking. The objective of this study was to address the feasibility of measuring 8-oxo-7, 8-dihydro-2-deoxyguanosine (8-OHdG) formation and human 8-oxoguanine DNA glycosylase (hOGG1) induction in peripheral blood mononuclear cell (PBMC) to assess oxidative deoxyribonucleic acid (DNA) damage in the lung of smoking COPD patients. MethodsPBMC were obtained from 412 participants including 129 smokers with COPD, 143 healthy smokers and 140 healthy non-smokers. Lung tissue specimens and PBMC were obtained from smoker COPD (n=12), healthy smokers (n=12) and healthy non-smokers (n=10). 8-OHdG and hOGG1 were detected, and correlation analysis was conducted for assessing the feasibility. ResultsOxidative DNA damage (8-OHdG formation) along with impaired induction of hOGG1 expression in the lung was a prominent feature for smokers COPD patients. PBMC originated from smokers COPD patients also displayed similar features to that of lung tissues. Correlation analysis suggests that PBMC could be used as a surrogate for oxidative DNA damage in lung of smokers COPD patients. Indeed, 8-OHdG levels in PBMC DNA were negatively correlated with lung function, while hOGG1 induction in PBMC was associated with improved lung function in smokers COPD patients. ConclusionsCOPD patients manifest oxidative DNA damage of 8-OHdG along with impaired hOGG1 expression in the lung, whereas 8-OHdG formation and hOGG1 induction in PBMC could be a biomarker of oxidative DNA damage in the lung. 8-OHdG is an indicator of ROS-induced oxidative DNA damage, and it can be repaired by hOGG1, a key enzyme in the repair of DNA damage. The 8-OHdG and hOGG1 in peripheral blood mononuclear cells are useful markers indicating oxidative DNA damage of lung tissues.
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