title: Endosulfan Induces CYP1A1 Expression Mediated through Aryl Hydrocarbon Receptor Signal Transduction by Protein Kinase C.
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, endosulfan-induced up-regulation of CYP1A1 is associated with AhR activation, which may be mediated by PKC-dependent pathways.
authors.affiliation: Drug & Disease Target Group, Division of Bioconvergence Analysis, Korea Basic Science Institute, Daejeon, Korea; Biological Analysis Science, University of Science and Technology, Daejeon, Korea.
authors.forename: Eun Hee
authors.initials: EH
authors.lastname: Han
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Hyung Gyun
authors.initials: HG
authors.lastname: Kim
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Toxicology, College of Pharmacy, Chungnam National University, Daejeon, Korea.
authors.forename: Hye Gwang
authors.initials: HG
authors.lastname: Jeong
keywords: Aryl hydrocarbon receptor; CYP1A1; Calcium; Endosulfan; Protein kinase C