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 SO2 on mitochondria and the corresponding molecular characterization in the lung. Male Wistar rats were exposed to 0, 3.5, 7, and 14 mg/m3 SO2 (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 SO2 inhalation. We showed that total mitochondrial DNA (mtDNA) content was significantly decreased in the lungs from rats exposed to SO2. Furthermore, SO2 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 SO2 exposure 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 SO2 inhalation. Such impairment may lead to cellular dysfunction and eventually lung diseases.

Sulfur Dioxide Contributes to the Cardiac and Mitochondrial Dysfunction in Rats.

Epidemiological studies have demonstrated an association between sulfur dioxide (SO2) and an increase of morbidity and mortality of cardiovascular diseases, such as ischemic heart disease, heart failure, and arrhythmia. Mitochondrion is the most sensitive organelle in myocardium of animals exposed to SO2 Here we study the molecular characterization of mitochondrial dysfunction in cardiac muscles of rat after SO2 exposure. We found that the cytochrome c oxidase (COX) activity, mitochondrial membrane potential (ΔΨm), ATP contents, mitochondrial DNA (mtDNA) contents, and mRNA expression of complexes IV and V subunits encoded by mtDNA were decreased after NaHSO3 treatment in vitro or SO2 inhalation in vivo The mitochondrial dysfunctions were accompanied by depressions of co-activator of peroxisome proliferator activated receptor gamma (PGC-1α), nuclear respiratory factor 1, and mitochondrial transcription factor A (TFAM) mRNA and protein. We observed swollen mitochondria and lower amounts of cristae in hearts of rats after 3.5 mg/m(3) SO2 inhalation for 30 days. Interestingly, NaHSO3 induced mitochondrial dysfunctions marked by ΔΨm and ATP reduction could be inhibited by an antioxidant N-acetyl-L-cysteine (NALC), accompanied by the restoration of transcriptional factors expressions. The cardiac mitochondrial dysfunctions could also be alleviated by overexpression of TFAM. SO2 induced abnormal left ventricular function was restored by NALC in vivo Our findings demonstrate that SO2 induces cardiac and mitochondrial dysfunction. And inhibition of reactive oxygen species and enhancing the transcriptional network controlling mitochondrial biogenesis can mitigate the SO2-induced mitochondrial dysfunction.

Sulfur dioxide inhalation stimulated mitochondrial biogenesis in rat brains.

Sulfur dioxide (SO(2)) is a common environmental pollutant. Mitochondria play essential roles in energy metabolism, generation of reactive oxygen species, and regulation of apoptosis in response to neuronal brain injury. It is of interest to observe the effect of SO(2) on mitochondrial function in brain. In the present study, male Wistar rats were housed in exposure chambers and treated with 3.5, 7 and 14mg/m(3) SO(2) for 4h/day for 30days, while control rats were exposed to filtered air in the same condition. Mitochondrial membrane potential (MMP) was assessed in cerebral mitochondria using the lipophilic cationic probe JC-1. The amount of ATP was measured by the luciferinluciferase method. Analyses of mitochondrial replication and transcription were performed by real time PCR. The protein levels were detected using Western blotting. Our results showed that cerebral mtDNA content was markedly increased in rats after SO(2) exposure. Paralleling the change in mtDNA content, MMP, ATP content, MDA level, CO1 & 4 and ATP6 & 8 expression, and cytochrome c oxidase activity were increased in rat cortex after SO(2) inhalation. Moreover, mitochondrial biogenesis was accompanied by increased expression of NRF1 and TFAM, whereas PGC-1α was not changed. We report for the first time increased mitochondrial biogenesis in brain of rats exposed to SO(2), which might be an adaptive response to mitochondrial depletion by oxidant damage.