Antioxidants alleviated sulfur dioxide-induced mitochondrial damage in rat hearts
XIA Jin1, QIN Guo-hua1,2, SANG Nan1
1. College of Environmental Science and Resources, Shanxi University, Taiyuan 030006, China;
2. Guangzhou Key Laboratory of Environmental Exposure and Health, School of Environment, Jinan University, Guangzhou 510632, China
Male Wistar rats were exposed to SO2 (7mg/m3) for 28 days, 4 hours per day in SO2 group. Rats in SO2+NALC group were exposed to SO2 and NALC (50mg/kg b.w., i.p.) every other day, which was dissolved in saline. Rats in control group were exposed to filtered air and saline. The mRNA levels of complexes IV and V subunits (CO1 & ATP6) and three mitochondrial transcript factors (PGC1-α, NRF1, TFAM) were analyzed by real-time RT-PCR after exposure. And the protein levels of the above three mitochondrial transcript factors were detected by Western blot. The results showed that the mRNA and protein expression levels of PGC1-α, NRF1and TFAM were decreased significantly after SO2 inhalation, combined with the down-regulations of CO1 & ATP6 on mRNA levels. But NALC could alleviate the depressions of these genes. It indicated that SO2 exposure could impact the transcription of mitochondria DNA through PGC1-α-NRF1-TFAM down-regulation, interfere the synthesis of important components of oxidative phosphorylation. The mechanism might be related to the production of free radicals. Antioxidants could be used to alleviate sulfur dioxide-induced mitochondrial damage in rat hearts.
Brook R D, Franklin B, Cascio W, et al. Air pollution and cardiovascular disease:A statement for healthcare professionals from the expert panel on population and prevention science of the American heart association[J]. Circulation, 2004,109:2655-2671.
[2]
Shapiro R. Genetic effects of bisulfite (sulfur dioxide)[J]. Mutat. Res., 1977,39:149-175.
[3]
Sunyer J, Ballester F, Tertre A L, et al. The association of daily sulfur dioxide air pollution levels with hospital admissions for cardiovascular diseases in Europe (the Aphea-Ⅱ study)[J]. Eur. Heart J, 2003,24:752-760.
[4]
Meng Z, Li R, Zhang X. Levels of sul?te in three organs from mice exposed to sulfur dioxide[J]. Inhal. Toxicol., 2005,17:309-313.
[5]
Meng Z, Qin G, Zhang B, et al. Oxidative damage of sulfur dioxide inhalation on lungs and hearts of mice[J]. Environ. Res., 2003,93:285-292.
[6]
Meng Z, Liu Y. Cell morphological ultrastructural changes in various organs from mice exposed by inhalation to sulfur dioxide[J]. Inhal. Toxicol., 2007,19:543-551.
[7]
Hadler H I, Cook G L. The mitochondrial activation of sulfate and arsenate and their role in carcinogenesis[J]. J Environ. Pathol. Toxicol., 1979,2(3):601-612.
[8]
Tsutsui H, Kinugawa S, Matsushima S. Oxidative stress and mitochondrial DNA damage in heart failure[J]. Circ. J, 2008,72:A31-A37.
[9]
Qin G, Wu M, Wang J, et al. Sulfur dioxide contributes to the cardiac and mitochondrial dysfunction in rats[J]. Toxicol. Sci., 2016,151(2):334-346.
[10]
Garnier A, Fortin D, Deloménie C, et al. Depressed mitochondrial transcription factors and oxidative capacity in rat failing cardiac and skeletal muscles[J]. J. Physiol., 2003,551:491-501.
[11]
Scarpulla R C. Nuclear activators and co-activators in mammalian mitochondrial biogenesis[J]. Biochim. Biophys. Acta, 2002,1576:1-14.
[12]
Newby D E, Mannucci P M, Tell G S. Expert position paper on air pollution and cardiovascular disease[J]. Eur. Heart J, 2015,36(2):83-93.
[13]
Meng Z. Oxidative damage of sulfur dioxide on various organs of mice:sulfur dioxide is a systemic oxidative damage agent[J]. Inhal. Toxicol., 2003,15:181-195.
[14]
Meng Z, Qin G, Zhang B. DNA damage in mice treated with sulfur dioxide by inhalation[J]. Environ. Mol. Mutagen., 2005,46:150-155.
[15]
Meng Z, Qin G, Zhang B, et al. DNA damaging effects of sulfur dioxide derivatives in cells from various organs of mice[J]. Mutagenesis, 2004,19(6):465-468.
[16]
Parisi M A, Clayton D A. Similarity of human mitochondrial transcription factor 1to high mobility group proteins[J]. Science, 1991,17,252(5008):965-969.
[17]
Scarpulla R C. Transcriptional paradigms in mammalian mitochondrial biogenesis and function[J]. Physiol. Rev., 2008,88(2):611-38.
[18]
Ryan M T, Hoogenraad N J. Mitochondrial-nuclear communications[J]. Annu. Rev. Biochem., 2007,76:701-22.
[19]
Finck B N, Kelly D P. Peroxisome proliferator-activated receptor gamma coactivator-1(PGC-1) regulatory cascade in cardiac physiology and disease[J]. Circulation, 2007,115(19):2540-8.
Dutch Expert Committee on Occupational Standards. Sulphur dioxide; health-based recommended occupational exposure limit, 5th ed[Z]. (ISBN 90-5549-507-7), Hague, The Netherlands:Health Council of the Netherlands Press, 2003.
[23]
Sang N, Yun Y, Li H, et al. SO2 inhalation contributes to the development and progression of ischemic stroke in the brain[J]. Toxicological Sciences, 2010,114(2):226-236.
[24]
Qin G, Wu M, Wang J, et al. Sulfur Dioxide Contributes to the Cardiac and Mitochondrial Dysfunction in Rats[J]. Toxicol. Sci., 2016, 151(2):334-346.
[25]
Ranguelova K, Rice A B, Khajo A, et al. Formation of reactive sulfite-derived free radicals by the activation of human neutrophils:an ESR study[J]. Free Radic. Biol. Med., 2012,52:1264-1271.
[26]
Velayutham M, Hemann C F, Cardounel A J, et al. Sulfite oxidase activity of cytochrome c:role of hydrogen peroxide[J]. Biochem. Biophys., 2016,5:96-104.
[27]
Nissar A U, Farrukh M R, Kaiser P J, et al. Effect of N-acetyl cysteine (NAC), an organosulfur compound from Allium plants, on experimentally induced hepatic prefibrogenic events in Wistar rat[J]. Phytomedicine, 2013,20(10):828-833.
Arany Z, Foo S Y, Ma Y. HIF-independent regulation of VEGF and angiogenesis by the transcriptional coactivator PGC-1α[J]. Nature, 2008,451(7181):1008-1012.
[30]
Lebrecht D, Walker U A. Role of mtDNA lesions in anthracycline cardiotoxicity[J]. Cardiovasc. Toxicol., 2007,7:108-113.
[31]
Zhang W, Liu Y, An Z, et al. Mediating effect of ROS on mtDNA damage and low ATP content induced by arsenic trioxide in mouse oocytes[J]. Toxicol., 2011,25:979-984.
[32]
Valerio A, Cardile A, Cozzi V, et al. TNF-alpha downregulates eNOS expression and mitochondrial biogenesis in fat and muscle of obese rodents[J]. J. Clin. Invest., 2006,116(10):2791-2798.
[33]
Sohn E J, Kim J, Hwang Y, et al. TGF-β suppresses the expression of genes related to mitochondrial function in lung A549cells[J]. Cell Mol. Biol., 2012,58(suppl.):1763-1767.
[34]
Yan W, Zhang H, Liu P, et al. Impaired mitochondrial biogenesis due to dysfunctional adiponectin-AMPK-PGC-1a signaling contributing to increased vulnerability in diabetic heart. Basic[J]. Res. Cardiol., 2013,108:329.
[35]
Zhu J H, Gusdon A M, Cimen H, et al. Impaired mitochondrial biogenesis contributes to depletion of functional mitochondria in chronic MPPt toxicity:Dual roles for ERK1/2[J]. Cell Death Dis., 2012,3(5):e312.