Binding and Activity of Polybrominated Diphenyl Ethers Sulfates to Thyroid Hormone Transport Proteins and Nuclear Receptors
Polybrominated diphenyl ethers (PBDEs) can be metabolized to hydroxylated PBDEs (OH-PBDEs), which play important roles in their disruption effects on thyroid hormone (TH) system. Recently, multiple in vitro studies suggested the OH-PBDEs might be further metabolic transformed to PBDE sulfates. However, the information about the bioactivity of PBDE sulfates metabolites is limited. In the present study, we explored the possible disruption effects of PBDE sulfates to TH system by studying their binding and activity towards TH transport proteins and nuclear receptors. We found PBDE sulfates could bind to two major TH transport proteins (thyroxine-binding globulin and transthyretin). Besides, PBDEs sulfates could also bind to two subtypes of TH nuclear receptors (TRα and TRβ) and showed agonistic activity towards the subsequent signaling pathway. Moreover, the PBDE sulfates showed higher binding potency to TH transport proteins and TRs compared with their corresponding OH-PBDE precursors. Molecular docking results showed replacement of hydroxyl groups with sulfate groups might lead to more hydrogen bond interactions with these proteins. Overall, our study suggested PBDE sulfates might disturb TH system by binding to TH transport proteins or TRs. Our finding indicated a possible mechanism for the TH system disruption effects of PBDEs through their sulfate metabolites.