title: The effect of hydroxylated polychlorinated biphenyl (OH-PCB) on thyroid hormone receptor (TR)-mediated transcription through native-thyroid hormone response element (TRE).
abstract: Polychlorinated biphenyls (PCBs) are known as environmental contaminants that may cause abnormal effect in various organs. We have previously reported that low dose of hydroxylated PCBs (OH-PCBs) including 4'-OH-2',3,3',4',5'-pentachloro biphenyl (4'-OH-PCB 106), suppressed thyroid hormone (TH) receptor (TR)-mediated transcription on several artificial TH-response elements (TREs) due to partial dissociation of TR from TRE. In the present study, we examined the effect of OH-PCB on TR-mediated transcription on native TRE-containing promoter, using malic enzyme (ME)-TRE. Transcriptional activity was measured by transient transfection based reporter gene assay in CV-1, fibroblast-derived clonal cells. TR-mediated transcription was suppressed by 4'-OH-PCB106 significantly and 4'-OH-PCB187 weakly, but not by 4'-OH-PCB165. To examine TR-TRE bindings under exposure of 4'-OH-PCB106, electrophoretic mobility shift assay (EMSA) was performed. In EMSA, TR was dissociated from ME-TRE by 4'-OH-PCB106. These findings suggest that OH-PCB may disrupt TR-mediated transcription on native promoter.
authors.affiliation: Department of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan.
authors.forename: Izuki
authors.initials: I
authors.lastname: Amano
authors.forename: Wataru
authors.initials: W
authors.lastname: Miyazaki
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Iwasaki
authors.forename: Noriaki
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Koibuchi
mesh_terms: D004305:Dose-Response Relationship, Drug; D006801:Humans; D006900:Hydroxylation; D008291:Malate Dehydrogenase; D011078:Polychlorinated Biphenyls / Q000737:chemistry / Q000494:pharmacology*; D011988:Receptors, Thyroid Hormone / Q000187:drug effects* / Q000502:physiology; D020218:Response Elements / Q000187:drug effects*; D013963:Thyroid Hormones / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects* / Q000502:physiology
chemical_list: D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D011078:Polychlorinated Biphenyls; D008291:Malate Dehydrogenase; C495394:malic enzyme 2; human