标题:The Effect of Hydroxylated Polychlorinated Biphenyl (OH-PCB) on Thyroid Hormone Receptor (TR)-mediated Transcription through Native-Thyroid Hormone Response Element (TRE)
出版社:National Institute of Occupational Safety and Health
摘要: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.