Enhanced Expression of Plasma Glutathione Peroxidase in the Thymus of Mice Treated with TCDD and Its Implication for TCDD-induced Thymic Atrophy

  • Cho, Hyun-Jin (Department of Biology, Changwon National University) ;
  • Hahn, Eun-Jin (Department of Biology, Changwon National University) ;
  • Hwang, Ju-Ae (Department of Biology, Changwon National University) ;
  • Hong, Min-Sun (Department of Biology, Changwon National University) ;
  • Kim, Sook-Kyung (Department of Biology, Changwon National University) ;
  • Pak, Hye-Ryun (Department of Biology, Changwon National University) ;
  • Park, Joo-Hung (Department of Biology, Changwon National University)
  • Received : 2006.01.11
  • Accepted : 2006.02.08
  • Published : 2006.04.30

Abstract

The potent environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), induces thymus atrophy in experimental animals. However, its mechanism of action is not fully understood. To gain insight into its immunosuppressive effect, Balb/c mice were intraperitoneally injected with TCDD ($30{\mu}g/kg$ body weight) and genes regulated by TCDD were identified using cDNA arrays [Park and Lee (2002)]. One of the regulated genes was that for plasma glutathione peroxidase (pGPx). Upon TCDD injection, pGPx mRNA levels in the thymus increased, in parallel with increases in GPx activity and the frequency of anti-human pGPx antibody-reactive cells. pGPX mRNA levels were also moderately up-regulated in the testis and spleen. This is the first report that a particular isotype of the glutathione peroxidase family is regulated by TCDD at both mRNA and protein levels. pGPx is expressed in various tissues in contact with body fluids, and detoxifies hydrogen peroxides and lipid hydroperoxides. It will be of interest to assess the role of pGPx in TCDD-induced thymic atrophy.

Keywords

Oxidative Stress;Plasma Glutathione Peroxidase;TCDD;Thymic Atrophy

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Burbach, K. M., Poland, A., and Bradfield, C. A. (1992) Cloning of the Ah-receptor cDNA reveals a distinctive ligand-activated transcription factor. Proc. Natl. Acad. Sci. USA 89, 8185-8189
  2. Burdon, R. H., Gill, V., and Rice-Evans, C. (1990) Oxidative stress and tumour cell proliferation. Free Radic. Res. Commun. 11, 65-76 https://doi.org/10.3109/10715769009109669
  3. Chu, F. F., Esworthy, R. S., Doroshow, J. H., Doan, K., and Liu, X. (1992) Expression of plasma glutathione peroxidase in human liver in addition to kidney, heart, lung, and breast in humans and rodents. Blood 79, 3233-3238
  4. El-far, M. A., Bakr, M. A., Farahat, S. E., and Abd El-Fattah, E. A. (2005) Glutathione peroxidase activity in patients with renal disorders. Clin. Exp. Nephrol. 9, 127-131 https://doi.org/10.1007/s10157-005-0343-1
  5. Hossain, A., Tsuchiyas, S., Minegishi, M., Osada, M., Ikawa, S., et al. (1998) The Ah receptor is not involved in 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated apoptosis in human leukemic T cell lines. J. Biol. Chem. 273, 19853-19858 https://doi.org/10.1074/jbc.273.31.19853
  6. Huang, H. S., Chen, C. J., Lu, H. S., and Chang, W. S. (1998) Identification of a lipooxygenase inhibitor in A431 cells as a phospholipid hydroperoxide glutathione peroxidase. FEBS Lett. 424, 22-26 https://doi.org/10.1016/S0014-5793(98)00130-6
  7. Kremer, J., Gleichmann, E., and Esser, C. (1994) Thymic stroma exposed to arylhydrocarbon receptor-binding xenobiotics fails to support proliferation of early thymocytes but induces differentiation. J. Immunol. 153, 2778-2786
  8. Lee, Y. S., Jin, D. Q., Park, S. H., Han, S. Y., Kim, H. S., et al. (2002) 2,3,7,8-tetrachlorodibenzo-p-dioxin inhibits proliferation of SK-N-SH human neuronal cells through decreased production of reactive species. Free Radic. Res. 36, 1283-1289 https://doi.org/10.1080/1071576021000016517
  9. Maser, R. L., Magenheimer, B. S., and Calvet, J. P. (1994) Mouse plasma glutathione peroxidase. J. Biol. Chem. 269, 27066-27073
  10. Poland, A. and Knutson, J. C. (1982) 2,3,7,8-tetrachlorodibenzop- dioxin and related halogenated aromatic hydrocarbons: examination of the mechanism of toxicity. Ann. Rev. Pharmacol. Toxicol. 22, 517-554 https://doi.org/10.1146/annurev.pa.22.040182.002505
  11. Ursini, F., Heim, S., Kiess, M., maiorino, M., Roveri, A., et al. (1999) Dual function of the selenoprotein PHGPx during sperm maturation. Science 285, 1393-1396 https://doi.org/10.1126/science.285.5432.1393
  12. Zachara, B. A., Ukleja-Adamowicz, M., Nartowicz, E., and Lecka, J. (2001) Increased plasma glutathione peroxidase activity in patients with acute myocardial infarction. Med. Sci. Monit. 7, 415-420
  13. Favreau, L. V. and Pickett, C. B. (1991) Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J. Biol. Chem. 266, 4556-4561
  14. Kerkvliet, N. L. and Burleson, G. R. (1994) Immunotoxicity of TCDD and related halogenated aromatic hydrocarbons; in Immonotoxicology and Immunopharmacology, Dean, J. H., Luster, M. I., Munson, A. E., and Kimber, I. (eds.), pp. 97-121, Raven Press, NY
  15. Lin, T. M., Ko, K., Moore, R. W., Buchanan, D. L., Cooke, P. S., et al. (2001) Role of the aryl hydrocarbon receptor in the development of control and 2,3,7,8-tetrachlorodibenzo-pdioxin-exposed male mice. J. Toxicol. Environ. Health 64, 327-342 https://doi.org/10.1080/152873901316981312
  16. Sarto, C., Frutiger, S., Cappellano, F., Sanchez, J.-C., Doro, G., et al. (1999) Modified expression of plasma glutathione peroxidase and maganese superoxide dismutase in human renal cell carcinoma. Electrophoresis 20, 3458-3466 https://doi.org/10.1002/(SICI)1522-2683(19991101)20:17<3458::AID-ELPS3458>3.0.CO;2-5
  17. Rushmore, T. H. and Pickett, C. B. (1990) Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene: characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. J. Biol. Chem. 265, 14648-14653
  18. Kuhn, H. and Borchert, A. (2002) Regulation of enzymatic lipid peroxidation: the interplay of peroxidizing and peroxide reducing enzymes. Free Radic. Biol. Med. 33, 154-172 https://doi.org/10.1016/S0891-5849(02)00855-9
  19. Park, J. H., Hahn, E. J., Kong, J. H., Cho, H. J., Yoon, C. S., et al. (2003) TCDD-induced apoptosis in EL-4 cells deficient of the aryl hydrocarbon receptor and down-regulation of IGFBP-6 prevented the apoptotic cell death. Toxicol. Lett. 145, 55-68 https://doi.org/10.1016/S0378-4274(03)00259-5
  20. Tham, D. M., Whitin, J. C., and Cohen, H. J. (2002) Increased expression of extracellular glutathione peroxidase in mice with dextran sodium sulfate-induced experimental colitis. Pediatr. Res. 51, 641-646 https://doi.org/10.1203/00006450-200205000-00016
  21. Minami, Y., Kono, T., Miyazaki, T., and Taniguchi, T. (1993) The IL-2 receptor complex: its structure, function, and target genes. Annu. Rev. Immunol. 11, 245-267 https://doi.org/10.1146/annurev.iy.11.040193.001333
  22. Park, J. H. and Lee, S. W. (2002) Up-regulated espression of genes encoding Hrk and IL-3R beta subunit by TCDD in vivo and in vitro. Toxicol. Lett. 129, 1-11 https://doi.org/10.1016/S0378-4274(01)00470-2
  23. Son, W. K., Lee, D. Y., Lee, S. H., Joo, W. A., and Kim, C. W. (2003) Analysis of proteins expressed in rat plasma exposed to dioxin using 2-dimensional gel electrophoresis. Proteomics 3, 2393-2401 https://doi.org/10.1002/pmic.200300605
  24. Sulentic, C. E. W., Holsapple, M. P., and Kaminski, N. E. (2000) Putative link between transcriptional regulation of IgM expression by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the aryl hydrocarbon receptor/dioxin-responsive enhancer signaling pathway. J. Pharmacol. Exp. Ther. 295, 705-716
  25. Devary, Y., Gottlieb, R. A., Lau, L. F., and Karin, M. (1991) Rapid and preferential activation of the c-jun gene during the mammalian UV response. Mol. Cell. Biol. 11, 2804-2811 https://doi.org/10.1128/MCB.11.5.2804
  26. Brigelius-Flohe, R. (1999) Tissue-specific function of individual glutathione peroxidase. Free Radic. Biol. Med. 27, 951-965. https://doi.org/10.1016/S0891-5849(99)00173-2
  27. Huff, J., Lucier, G., and Tritscher, A. (1994) Carcinogenicity of TCDD: experimental, mechanistic, and epidemiologic evidence. Annu. Rev. Pharmacol. Toxicol. 34, 343-372 https://doi.org/10.1146/annurev.pa.34.040194.002015
  28. Kamath, A. B., Camacho, I., Nagarkatti, P. S., and Nagarkatti, M. (1999) Role of Fas-Fas ligand interactions in 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD)-induced immunotoxicity: increased resistance of thymocytes from Fas-deficient (lpr) and Fas ligand-defective (gld) mice to TCDD-induced toxicity. Toxicol. Appl. Pharmacol. 160, 141-155 https://doi.org/10.1006/taap.1999.8753
  29. Schwabb, V., Baud, E., Ghyselinck, N., Mattei, M. G., Dafaure, J. P., et al. (1995) Cloning of the mouse gene encoding plasma glutathione peroxidase: organization, sequence, and chromosomal localization. Gene 167, 25-31 https://doi.org/10.1016/0378-1119(95)00551-X
  30. Denison, M. S., Fisher, J. M., and Whitlock, J. P. Jr. (1988) The DNA recognition site for the dioxin-Ah receptor complex. Nucleotide sequence and functional analysis. J. Biol. Chem. 263, 17221-17224
  31. Latchoumycandane, C., Chitra, K. C., and Mathur, P. P. (2003) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induces oxidative stress in the epididymis and epididymal sperm of adult rats. Arch. Toxicol. 77, 280-284 https://doi.org/10.1007/s00204-003-0439-x
  32. Takahashi, K., Avissar, N., Whitin, J., and Cohen, H. (1987) Purification and characterization of human plasma glutathione peroxidase: a selenoglycoprotein distinct from the known cellular enzyme. Arch. Biochem. Biophys. 256, 677-686 https://doi.org/10.1016/0003-9861(87)90624-2
  33. Williams, K., Frayne, J., and Hall, L. (1998) Expression of extracellular glutathione peroxidase type 5 (GPx5) in the rat male reproductive tract. Mol. Human Reprod. 4, 841-848 https://doi.org/10.1093/molehr/4.9.841
  34. Staples, J. E., Fiore, N. C., Frazier, D. E. Jr., Gasiewicz, T. A., and Silverstone, A. E. (1998) Overexpression of the antiapoptotic oncogene, bcl-2, in the thymus does not prevent thymic atrophy induced by estradiol or 2,3,7,8-tetrachlorodibenzo- p-dioxin. Toxicol. Appl. Pharmacol. 151, 200-210 https://doi.org/10.1006/taap.1998.8446
  35. Chu, F. F. and Esworthy, R. S. (1995) The expression of an intestinal form of glutathione peroxidase (GSHPx-GI) in rat intestinal epithelium. Arch. Biochem. Biophys. 323, 288-294 https://doi.org/10.1006/abbi.1995.9962
  36. Hassoun, E. A., Al-Ghafri, M., and Abushaban, A. (2003) The role of antioxidant enzymes in TCDD-induced oxidative stress in various brain regions of rats after subchronic exposure. Free Radic. Biol. Med. 35, 1028-1036 https://doi.org/10.1016/S0891-5849(03)00458-1
  37. Alsharif, N. Z. and Hassoun, E. A. (2004) Protective effects of vitamin A and vitamin E succinate against 2,3,7,8-tetrachlorodibenzo- p-dioxin (TCDD)-induced body wasting, hepatomegaly, thymic atrophy, production of reactive oxygen species and DNA damage in C57BL/6J mice. Basic Clin. Pharmacol. Toxicol. 95, 131-138
  38. Park, J. H., Lee, S. W., Kim, I. T., Shin, B. S., Cheong, S. W., et al. (2001) TCDD-up-regulation of IGFBP-6 and IL-5R alpha subunit genes in vivo and in vitro. Mol. Cells 12, 372-379
  39. Yoshimura, S., Suemizu, H., Nomoto, Y., Sakai, H., Katuoka, Y., et al. (1996) Plasma glutathione peroxidase deficiency caused by renal disfunction. Nephron 73, 207-211 https://doi.org/10.1159/000189042
  40. Shibanuma, M., Kuroki, T., and Nose, K. (1990) Stimulation bu hydrogen peroxide of DNA synthesis, competence family gene expression and phosphorylation of a specific protein in quiescent Balb/c 3T3 cells. Oncogene 5, 1025-1032
  41. Singh, A. K. and Shi chi, H. (1998) A novel glutathione peroxidase in bovine eye. J. Biol. Chem. 273, 26171-26178 https://doi.org/10.1074/jbc.273.40.26171
  42. Swanson, H. I. and Bradfield, C. A. (1993) The AH-receptor: Genetics, structure and function. Pharmacogenetics 3, 213-230 https://doi.org/10.1097/00008571-199310000-00001
  43. Kolluri, S. K., Weiss, C., Koff, A., and Gottlicher M. (1999) p27Kip1 induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes Dev. 13, 1742-1753 https://doi.org/10.1101/gad.13.13.1742
  44. Nose, K., Shibanuma, M., Kikuchi, K., Kageyama, H., Sakiyama, S., et al. (1991) Transcriptional activation of early response genes by hydrogen peroxide in a mouse osteoblastic cell line. Eur. J. Biochem. 201, 99-106 https://doi.org/10.1111/j.1432-1033.1991.tb16261.x
  45. Pfeifer, H., Conrad, M., Roethlein, D., Kyriakopoulous, A., Brielmeier, M., et al. (2001) Identification of a specific sperm nuclei selenoenzyme necessary for protamine thiol cross-linking during sperm formation. FASEB J. 15, 1236-1238 https://doi.org/10.1096/fj.00-0655fje
  46. Tritscher, A. M., Goldstein, J. A., Portier, C. J., McCoy, Z., Clark, G. C., et al. (1992) Dose-response relationships for chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin in a rat tumor promotion model: quantitation and immunolocalization of CYP1A1 and CYP1A2 in the liver. Cancer Res. 52, 3436-3442
  47. Tan, Z., Chang, X., Puga, A., and Xia, Y. (2002) Activation of mitogen-activated protein kinases (MAPKs) by aromatic hydrocarbons: role in the regulation of aryl hydrocarbon receptor (AHR) function. Biochem. Pharmacol. 64, 771-780 https://doi.org/10.1016/S0006-2952(02)01138-3
  48. Bukowska, B. (2004) Damage to erythrocytes caused by 2,3,7,8- tetrachlorodibenzo-p-dioxin (in vitro). Cell. Mol. Bio. Lett. 9, 261-270