title: Sulfur Dioxide Contributes to the Cardiac and Mitochondrial Dysfunction in Rats.
abstract: 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.
authors.affiliation: The College of Environmental Science and Resources, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Guohua
authors.initials: G
authors.lastname: Qin
authors.affiliation: The College of Environmental Science and Resources, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Meiqiong
authors.initials: M
authors.lastname: Wu
authors.affiliation: The College of Environmental Science and Resources, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Jiaoxia
authors.initials: J
authors.lastname: Wang
authors.affiliation: The College of Environmental Science and Resources, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Zhifang
authors.initials: Z
authors.lastname: Xu
authors.affiliation: The College of Environmental Science and Resources, Shanxi University, Taiyuan, Shanxi, 030006, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Xia
authors.affiliation: The College of Environmental Science and Resources, Shanxi University, Taiyuan, Shanxi, 030006, China sangnan@sxu.edu.cn.
authors.forename: Nan
authors.initials: N
authors.lastname: Sang
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D066126:Cardiotoxicity; D002460:Cell Line; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D003576:Electron Transport Complex IV / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D019570:Inhalation Exposure; D008297:Male; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D025261:Mitochondrial Proton-Translocating ATPases / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018384:Oxidative Stress / Q000187:drug effects; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013447:Sulfites / Q000633:toxicity*; D013458:Sulfur Dioxide / Q000633:toxicity*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004272:DNA, Mitochondrial; D017382:Reactive Oxygen Species; D013447:Sulfites; C489030:Tfam protein, rat; D014157:Transcription Factors; C021983:complex V (mitochondrial oxidative phosphorylation system); D013458:Sulfur Dioxide; C569244:sodium hydrogen sulfite; D003576:Electron Transport Complex IV; D025261:Mitochondrial Proton-Translocating ATPases
keywords: TFAM; cardiac muscles.; mitochondria; reactive oxygen species; sulfur dioxide