Abstract
CYP1A1 is a phase I xenobiotic-metabolizing enzyme whose expression is mainly driven by AhR. Endosulfan is an organochlorine pesticide used agriculturally for a wide range of crops. In this study, we investigated the effect of endosulfan on CYP1A1 expression and regulation. Endosulfan significantly increased CYP1A1 enzyme activity as well as mRNA and protein levels. In addition, endosulfan markedly induced XRE transcriptional activity. CH-223191, an AhR antagonist, blocked the endosulfan-induced increase in CYP1A1 mRNA and protein expression. Moreover, endosulfan did not induce CYP1A1 gene expression in AhR-deficient mutant cells. Furthermore, endosulfan enhanced the phosphorylation of calcium calmodulin (CaM)-dependent protein kinase (CaMK) and protein kinase C (PKC). In conclusion, endosulfaninduced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways.
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Nelson, D.R., Koymans, L., Kamataki, T., Stegeman, J.J., Feyereisen, R., Waxman, D.J., Waterman, M.R., Gotoh, O., Coon, M.J., Estabrook, R.W., Gunsalus, I.C. and Nebert, D.W. (1996) P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics, 6, 1–42.
Dipple, A. (1994) Reactions of polycyclic aromatic hydrocarbons with DNA. IARC Sci. Publ., 125, 107–129.
Han, E.H., Kim, H.G., Im, J.H., Jeong, T.C. and Jeong, H.G. (2009) Up-regulation of CYP1A1 by rutaecarpine is dependent on aryl hydrocarbon receptor and calcium. Toxicology, 266, 38–47.
Denis, M., Cuthill, S., Wikström, A.C., Poellinger, L. and Gustafsson, J.A. (1988) Association of the dioxin receptor with the Mr 90,000 heat shock protein: a structural kinship with the glucocorticoid receptor. Biochem. Biophys. Res. Commun., 155, 801–807.
Perdew, G.H. (1988) Association of the Ah receptor with the 90-kDa heat shock protein. J. Biol. Chem., 263, 13802–13805.
Kazlauskas, A., Poellinger, L. and Pongratz, I. (1999) Evidence that the co-chaperone p23 regulates ligand responsiveness of the dioxin (Aryl hydrocarbon) receptor. J. Biol. Chem., 274, 13519–13524.
Meyer, B.K., Pray-Grant, M.G., Vanden Heuvel, J.P. and Perdew, G.H. (1998) Hepatitis B virus X-associated protein 2 is a subunit of the unliganded aryl hydrocarbon receptor core complex and exhibits transcriptional enhancer activity. Mol. Cell. Biol., 18, 978–988.
Eguchi, H., Ikuta, T., Tachibana, T., Yoneda, Y. and Kawajiri, K. (1997) A nuclear localization signal of human aryl hydrocarbon receptor nuclear translocator/hypoxia-inducible factor 1beta is a novel bipartite type recognized by the two components of nuclear pore-targeting complex. J. Biol. Chem., 272, 17640–17647.
Kolluri, S.K., Weiss, C., Koff, A. and Göttlicher, M. (1999) p27(Kip1) induction and inhibition of proliferation by the intracellular Ah receptor in developing thymus and hepatoma cells. Genes Dev., 13, 1742–1753.
Omurtag, G.Z., Tozan, A., Sehirli, A.O. and Sener, G. (2008) Melatonin protects against endosulfan-induced oxidative tissue damage in rats. J. Pineal Res., 44, 432–438.
Sethunathan, N., Megharaj, M., Chen, Z., Singh, N., Kookana, R.S. and Naidu, R. (2002) Persistence of endosulfan and sulfate in soil as affected by moisture regime and organic matter addition. Bull. Environ. Contam. Toxicol., 68, 725–731.
Sunderam, R.I.M., Cheng, D.M.H. and Thompson, G.B. (1992) Toxicity of endosulfan to native and introduced fish in Australia. Environ. Toxicol. Chem., 11, 1469–1476.
Sinha, N., Narayan, R. and Saxena, D.K. (1997) Effect of endosulfan on testis of growing rats. Bull. Environ. Contam. Toxicol., 58, 79–86.
Chaudhuri, K., Selvaraj, S. and Pal, A.K. (1999) Studies on the genotoxicology of endosulfan in bacterial system. Mutat. Res., 439, 63–67.
Paul, V. and Balasubramaniam, E. (1997) Effect of single and repeated administration of endosulfan on behaviour and its interaction with centrally acting drugs in experimental animals. Environ. Toxicol. Pharmacol., 3, 151–157.
Hincal, F., Gurbay, A. and Giray, B. (1995) Induction of lipid peroxidation and alteration of glutathione redox status by endosulfan. Biol. Trace Elem. Res., 47, 321–326.
Han, E.H., Hwang, Y.P., Kim, H.G. and Jeong, H.G. (2007) Inflammatory effect of endosulfan via NF-kappaB activation in macrophages. Biochem. Biophys. Res. Commun., 355, 860–865.
Kim, K.W. and Chung, Y.H. (2013) Hepatotoxicity in rats treated with dimethylformamide or toluene or both. Toxicol. Res., 29, 187–193.
Lee, C.M., Yoon, M.S. and Kim, Y.C. (2015) Effects of pueraria lobata root ethanol extract on adipogenesis and lipogenesis during 3T3-L1 differentiation into adipocytes. Toxicol. Res., 31, 191–201.
Kim, H.G., Han, E.H. and Jeong H.G. (2008) Effect of troglitazone on CYP1A1 induction. Toxicology, 246, 166–171.
Kim, S.H., Henry, E.C., Kim, D.K., Kim, Y.H., Shin, K.J., Han, M.S., Lee, T.G., Kang, J.K., Gasiewicz, T.A., Ryu, S.H. and Suh, P.G. (2006) Novel compound 2-methyl-2H-pyrazole-3-carboxylic acid (2-methyl-4-o-tolylazo-phenyl)-amide (CH-223191) prevents 2,3,7,8-TCDD-induced toxicity by antagonizing the aryl hydrocarbon receptor. Mol. Pharmacol., 69, 1871–1878.
Iida, M., Bak, S.M., Murakami, Y., Kim, E.Y. and Iwata, H. (2014) Transient suppression of AHR activity in early red seabream embryos does not prevent the disruption of peripheral nerve projection by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Aquat. Toxicol., 154, 39–47.
Tan, Z., Huang, M., Puga, A. and Xia, Y. (2004) A critical role for MAP kinases in the control of Ah receptor complex activity. Toxicol. Sci., 82, 80–87.
Rendie, S. and Di Carlo, F.J. (1997) Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab. Rev., 29, 413–580.
Denison, M.S. and Whitlock, J.P. (1995) Xenobiotic-inducible transcription of cytochrome P450 genes. J. Biol. Chem., 270, 18175–18178.
Chen, Y.H. and Tukey, R.H. (1996) Protein kinase C modulates regulation of the CYP1A1 gene by the aryl hydrocarbon receptor. J. Biol. Chem., 271, 26261–26266.
Machemer, D.E. and Tukey, R.H. (2005) The role of protein kinase C in regulation of TCDD-mediated CYP1A1 gene expression. Toxicol. Sci., 87, 27–37.
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Han, E.H., Kim, H.G., Lee, E.J. et al. Endosulfan Induces CYP1A1 Expression Mediated through Aryl Hydrocarbon Receptor Signal Transduction by Protein Kinase C. Toxicol Res. 31, 339–345 (2015). https://doi.org/10.5487/TR.2015.31.4.339
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DOI: https://doi.org/10.5487/TR.2015.31.4.339