Title: Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes.
Authors: Li, Xiaobo; Yang, Hongbao; Sun, Hao; Lu, Runze; Zhang, Chengcheng; Gao, Na; Meng, Qingtao; Wu, Shenshen; Wang, Susanna; Aschner, Michael; Wu, Jiong; Tang, Boping; Gu, Aihua; Kay, Steve A; Chen, Rui
Published In Proc Natl Acad Sci U S A, (2017 11 07)
Abstract: 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.
PubMed ID: 29078374
MeSH Terms: Adenine/analogs & derivatives; Adenine/pharmacology; Aged; Animals; Autophagy/drug effects; CCAAT-Enhancer-Binding Proteins/metabolism; Cell Line; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Female; Genes, Mitochondrial/drug effects; Humans; Lung/drug effects; Lung/metabolism; Male; Mice; Mice, Inbred C57BL; Middle Aged; Mitochondria/drug effects*; Mitochondria/metabolism*; NADH Dehydrogenase/metabolism*; Particulate Matter/pharmacology*; Pulmonary Disease, Chronic Obstructive/drug therapy; Pulmonary Disease, Chronic Obstructive/metabolism; Pulmonary Emphysema/chemically induced*; Pulmonary Emphysema/drug therapy*; Pulmonary Emphysema/metabolism; Taurine/therapeutic use*