Environmental Analysis Health and Toxicology

The Korean Society of Environmental Health and Toxicology (환경독성보건학회)
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Effect of Dioxin on the Change of Mitochondrial Inner Membrane Potential and the Induction of ROS

다이옥신이 미토콘드리아 내막의 전위차 변화 및 ROS 생성에 미치는 영향

  • 조일영 (이화여자대학교 약학대학) ;
  • 신윤용 (이화여자대학교 약학대학)
  • Published : 2009.03.31
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Abstract

Among the toxicants in the environment dioxin-like compounds, including TCDD(2,3,7,8-Tetrachlorodibenzo-p-Dioxin), are well known as carcinogen and teratogen. TCDD the most toxic of these compounds, may result in a wide variety of adverse health effects in humans and environment, including carconogenesis, hepatotoxicity, teratogenesis, and immunotoxicity. Also TCDD increases superoxide, peroxide radicals and induces oxidative stress that leads to breakage of DNA single-strand and mitochondrial dysfunction. Recently, there have been reports that persistent organic pollutants(POPs) may be causing metabolic disease through mitochondrial toxicity. In order to examine if dioxin brings about toxicity on mitochondria directly, we measured the change of the mitochondrial membrane potential after exposure to TCDD using JC-1 dye. After short time exposure of dioxin, mitochondrial depolarization was observed but it recovered to the control level immediately. This TCDD effect on mitochondrial membrane potential was not correlated either to the production of reactive oxygen species(ROS) or extracellular $Ca^{2+}$ by TCDD. Less than 2 hours exposure of TCDD did not show any change in ROS production but 0.25 nM TCDD for 48 hours or 0.5 nM TCDD for 12 hours exposure did increase in ROS production. Under these conditions of ROS production by TCDD, no changes in the mitochondrial membrane potential by TCDD was observed.

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References

  1. Arisawa K, Takeda H and Mikasa H. Background exposure to PCDDs/PCDFs/PCBs and its potential health effects: a review of epidemiologic studies, J Med Invest 2005; 52 (1-2): 10-21 https://doi.org/10.2152/jmi.52.10
  2. Biswas G, Srinivasan S, Anandatheerthavarada HK and Avadhani NG. Dioxin-mediated tumor progression through activation of mitochondria-to-nucleus stress signaling, Proc Natl Acad Sci USA 2008; 105(1): 186-191 https://doi.org/10.1073/pnas.0706183104
  3. Carosio R, Zuccari G, Orienti I, Mangraviti S and Montaldo PG. Sodium ascorbate induces apoptosis in neuroblastoma cell lines by interfering with iron uptake, Mol Cancer 2007; 6: 55 https://doi.org/10.1186/1476-4598-6-55
  4. Davis D and Safe S. Immunosuppressive activities of polychlorinated biphenyls in C57BL/6N mice: structure-activity relationships as Ah receptor agonists and partial antagonists, Toxicology 1990; 63(1): 97-111 https://doi.org/10.1016/0300-483X(90)90072-O
  5. Hassoun EA, Wang H, Abushaban A and Stohs SJ. Induction of oxidative stress in the tissues of rats after chronic exposure to TCDD, 2,3,4,7,8-pentachlorodibenzofuran, and 3,3′,4,4′,5-pentachlorobiphenyl, J Toxicol Environ Health A 2002; 65(12): 825-842 https://doi.org/10.1080/00984100290071054
  6. Knerr S, Schaefer J, Both S, Mally A, Dekant W and Schrenk D. 2,3,7,8-Tetrachlorodibenzo-p-dioxin induced cytochrome P450s alter the formation of reactive oxygen species in liver cells, Mol Nutr Food Res 2006; 50(4-5): 378-384 https://doi.org/10.1002/mnfr.200500183
  7. Lin PH, Lin CH, Huang CC, Chuang MC and Lin P. 2,3,7,8- Tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress, DNA strand breaks, and poly (ADP-ribose) polymerase-1 activation in human breast carcinoma cell lines, Toxicol Lett 2007; 172(3): 146-158 https://doi.org/10.1016/j.toxlet.2007.06.003
  8. Lin SY, Lai WW, Chou CC, Kuo HM, Li TM, Chung JG and Yang JH. Sodium ascorbate inhibits growth via the induction of cell cycle arrest and apoptosis in human malignant melanoma A375.S2 cells, Melanoma Res 2006; 16: 509-519 https://doi.org/10.1097/01.cmr.0000232297.99160.9e
  9. Mitrou PI, Dimitriadis G and Raptis SA. Toxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin and related compounds, Eur J Intern Med 2001; 12(5): 406-411 https://doi.org/10.1016/S0953-6205(01)00146-7
  10. Orrenius S, Zhivotovsky B and Nicotera P. Regulation of cell death: the calcium-apoptosis link, Nat Rev Mol Cell Biol 2003; 4(7): 552-565 https://doi.org/10.1038/nrm1150
  11. Park JY, Shigenaga MK and Ames BN. Induction of cytochrome P4501A1 by 2,3,7,8-tetrachlorodibenzo-p-dioxin or indolo (3,2-b)carbazole is associated with oxidative DNA damage, Proc Natl Acad Sci USA 1996; 93(6): 2322-2327 https://doi.org/10.1073/pnas.93.6.2322
  12. Piaggi S, Novelli M, Martino L, Masini M, Raggi C, Orciuolo E, Masiello P, Casini A and De Tata V. Cell death and impairment of glucose-stimulated insulin secretion induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the beta-cell line INS-1E, Toxicol Appl Pharmacol 2007; 220(3): 333-340 https://doi.org/10.1016/j.taap.2007.01.017
  13. Poland A and Knutson JC. 2,3,7,8-tetrachlorodibenzo-p-dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity, Annu Rev Pharmacol Toxicol 1982; 22: 517-554 https://doi.org/10.1146/annurev.pa.22.040182.002505
  14. Senft AP, Dalton TP, Nebert DW, Genter MB, Hutchinson RJ and Shertzer HG. Dioxin increases reactive oxygen production in mouse liver mitochondria, Toxicol Appl Pharmacol 2002a; 178(1): 15-21 https://doi.org/10.1006/taap.2001.9314
  15. Senft AP, Dalton TP, Nebert DW, Genter MB, Puga A, Hutchinson RJ, Kerzee JK, Uno S and Shertzer HG. Mitochondrial reactive oxygen production is dependent on the aromatic hydrocarbon receptor, Free Radic Biol Med 2002b; 33(9): 1268-1278 https://doi.org/10.1016/S0891-5849(02)01014-6
  16. Shen D, Dalton TP, Nebert DW and Shertzer HG. Glutathione redox state regulates mitochondrial reactive oxygen production, J Biol Chem 2005; 280(27): 25305-25312 https://doi.org/10.1074/jbc.M500095200
  17. Tiernan TO, Taylor ML, Garrett JH, VanNess GF, Solch JG, Wagel DJ, Ferguson GL and Schecter A. Sources and fate of polychlorinated dibenzodioxins, dibenzofurans and related compounds in human environments, Environ Health Perspect 1985; 59: 145-158 https://doi.org/10.2307/3429887
  18. Vergun O and Reynolds IJ. Fluctuations in mitochondrial membrane potential in single isolated brain mitochondria: modulation by adenine nucleotides and $Ca^{2+}$, Biophys J 2004; 87: 3585-3593 https://doi.org/10.1529/biophysj.104.042671