The effect of hydroxylated polychlorinated biphenyl (OH-PCB) on thyroid hormone receptor (TR)-mediated transcription through native-thyroid hormone response element (TRE).
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.
Amano
Izuki
I
Department of Integrative Physiology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan.
Miyazaki
Wataru
W
Iwasaki
Toshiharu
T
Shimokawa
Noriaki
N
Koibuchi
Noriyuki
N
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
D011988:Receptors, Thyroid Hormone; D013963:Thyroid Hormones; D011078:Polychlorinated Biphenyls; D008291:Malate Dehydrogenase; C495394:malic enzyme 2; human