Qin Guohua, Wang Jiaoxia, Sang Nan
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.
Environ Sci Pollut Res Int. 2017 Jan;24(3):2527-2534. doi: 10.1007/s11356-016-7859-7. Epub 2016 Nov 8.
Epidemiological studies show that sulfur dioxide (SO), 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 SO on mitochondria and the corresponding molecular characterization in the lung. Male Wistar rats were exposed to 0, 3.5, 7, and 14 mg/m SO (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 SO inhalation. We showed that total mitochondrial DNA (mtDNA) content was significantly decreased in the lungs from rats exposed to SO. Furthermore, SO repressed 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 SO exposure induced mitochondrial dysfunction in rat lungs. Both nDNA and mtDNA are involved in SO-induced depression of mitochondrial biogenesis in the lungs. There might be a tissue-specific response of mitochondrial biosynthesis to SO inhalation. Such impairment may lead to cellular dysfunction and eventually lung diseases.
流行病学研究表明，主要空气污染物二氧化硫（SO₂）与呼吸道疾病的发病率和死亡率相关。本研究的目的是确定SO₂对肺线粒体的影响及相应的分子特征。将雄性Wistar大鼠暴露于0、3.5、7和14mg/m³的SO₂（每天4小时，共30天）。吸入SO₂后，在大鼠肺中观察到线粒体功能障碍，包括细胞色素c氧化酶（COX）活性降低和线粒体膜电位（MMP）降低。我们发现，暴露于SO₂的大鼠肺中总线粒体DNA（mtDNA）含量显著降低。此外，SO₂抑制了由核DNA（nDNA）和mtDNA编码的复合物IV和V亚基的表达。而且，这些变化伴随着三种调节因子的抑制：过氧化物酶体增殖物激活受体γ共激活因子1α（PGC-1α）、核呼吸因子1（NRF1）和线粒体转录因子A（TFAM）。这些发现表明，暴露于SO₂会诱导大鼠肺线粒体功能障碍。nDNA和mtDNA均参与了SO₂诱导的肺线粒体生物合成抑制。线粒体生物合成对吸入SO₂可能存在组织特异性反应。这种损伤可能导致细胞功能障碍并最终引发肺部疾病。
