Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes.
Xiaobo LiHongbao YangHao SunRunze LuChengcheng ZhangNa GaoQingtao MengShenshen WuSusanna WangMichael AschnerJiong WuBoping TangAihua GuSteve A KayRui ChenPublished in: Proceedings of the National Academy of Sciences of the United States of America (2017)
Chronic obstructive pulmonary disease (COPD) has been linked to particulate matter (PM) exposure. Using transcriptomic analysis, we demonstrate that diesel exhaust particles, one of the major sources of particulate emission, down-regulated genes located in mitochondrial complexes I and V and induced experimental COPD in a mouse model. 1-Nitropyrene was identified as a major toxic component of PM-induced COPD. In the panel study, COPD patients were found to be more susceptible to PM than individuals with normal lung function due to an increased inflammatory response. Mechanistically, exposure to PM in human bronchial epithelial cells led to a decline in CCAAT/enhancer-binding protein alpha (C/EBPα), which triggered aberrant expression of NADH dehydrogenase genes and ultimately led to enhanced autophagy. ATG7-deficient mice, which have lower autophagy rates, were protected from PM-induced experimental COPD. Using metabolomics analysis, we further established that treatment with taurine and 3-methyladenine completely restored mitochondrial gene expression levels, thereby ameliorating the PM-induced emphysema. Our studies suggest a potential therapeutic intervention for the C/EBPα/mitochondria/autophagy axis in PM-induced COPD.
Keyphrases
- particulate matter
- lung function
- air pollution
- chronic obstructive pulmonary disease
- diabetic rats
- high glucose
- oxidative stress
- gene expression
- binding protein
- inflammatory response
- cell death
- drug induced
- heavy metals
- mouse model
- endoplasmic reticulum stress
- signaling pathway
- dna methylation
- drinking water
- transcription factor
- newly diagnosed
- reactive oxygen species