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Proc Natl Acad Sci U S A. 2017 Nov 7;114(45):E9655-E9664. doi: 10.1073/pnas.1712465114. Epub 2017 Oct 25.

Taurine ameliorates particulate matter-induced emphysema by switching on mitochondrial NADH dehydrogenase genes.

Author information

1
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China.
2
Center for New Drug Safety Evaluation and Research, China Pharmaceutical University, Nanjing 211198, China.
3
Department of Neurology, University of Southern California, Los Angeles, CA 90089.
4
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461.
5
Department of Life Science, Zhejiang Technology University, Hangzhou 310018, China.
6
Jiangsu Key Laboratory for Bioresources of Saline Soils, Jiangsu Synthetic Innovation Center for Coastal Bioagriculture, Yancheng Teachers University, Yancheng 224002, China.
7
State Key Laboratory of Reproductive Medicine, Institute of Toxicology, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
8
Department of Neurology, University of Southern California, Los Angeles, CA 90089; stevekay@usc.edu rui.chen@seu.edu.cn.
9
Key Laboratory of Environmental Medicine Engineering, Ministry of Education, School of Public Health, Southeast University, Nanjing 210009, China; stevekay@usc.edu rui.chen@seu.edu.cn.
10
Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 511436, China.

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.

KEYWORDS:

autophagy; chronic obstructive pulmonary disease; mitochondria; particulate matter; taurine

PMID:
29078374
PMCID:
PMC5692577
DOI:
10.1073/pnas.1712465114
[Indexed for MEDLINE]
Free PMC Article

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