Sulfur dioxide inhibits expression of mitochondrial oxidative phosphorylation genes encoded by both nuclear DNA and mitochondrial DNA in rat lungs.
Epidemiological studies show that sulfur dioxide (SO2), a major air pollutant, is associated with the morbidity and mortality of respiratory tract diseases. The aim of the present study was to determine the effects of SO2on mitochondria and the corresponding molecular characterization in the lung. Male Wistar rats were exposed to 0, 3.5, 7, and 14 mg/m3SO2(4 h/day, 30 days). Mitochondrial dysfunction including decreases of cytochrome c oxidase (COX) activity and mitochondrial membrane potential (MMP) was observed in the lungs of rats after SO2inhalation. We showed that total mitochondrial DNA (mtDNA) content was significantly decreased in the lungs from rats exposed to SO2. Furthermore, SO2repressed the expression of complex IV and V subunits encoded by both nuclear DNA (nDNA) and mtDNA. Moreover, such changes were accompanied by depressions of three regulatory factors: peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The findings suggest that SO2exposure induced mitochondrial dysfunction in rat lungs. Both nDNA and mtDNA are involved in SO2-induced depression of mitochondrial biogenesis in the lungs. There might be a tissue-specific response of mitochondrial biosynthesis to SO2inhalation. Such impairment may lead to cellular dysfunction and eventually lung diseases.
College of Environmental Science and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, China.|Guangzhou Key Laboratory of Environmental Exposure and Health, School of Environment, Jinan University, Guangzhou, 510632, China.
Guohua
G
Qin
College of Environmental Science and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, China.
Jiaoxia
J
Wang
College of Environmental Science and Resources, Research Center of Environment and Health, Shanxi University, Taiyuan, Shanxi, 030006, China. sangnan@sxu.edu.cn.
Nan
N
Sang
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins / Q000378:metabolism; D003576:Electron Transport Complex IV / Q000235:genetics; D008168:Lung / Q000378:metabolism; D008297:Male; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000378:metabolism; D024101:Mitochondrial Proteins; D010085:Oxidative Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013458:Sulfur Dioxide / Q000633:toxicity*; D014157:Transcription Factors
D000393:Air Pollutants; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D013458:Sulfur Dioxide; D003576:Electron Transport Complex IV
Cytochrome c oxidase; F1F0 ATPase; Lung; Mitochondria; Mitochondrial DNA; Sulfur dioxide