甲状腺
斑马鱼
体内
甲状腺激素受体
生物信息学
化学
内分泌系统
激素
受体
视黄醇X受体
多溴联苯醚
内科学
核受体
内分泌学
生物
药理学
转录因子
生物化学
遗传学
医学
污染物
基因
有机化学
作者
Penghao Wei,Yihua Xiao,Changqing Liu,Bing Yan
标识
DOI:10.1016/j.aquatox.2023.106535
摘要
Conventional thyroid-disrupting chemicals (TDCs) such as polybrominated diphenyl ethers, polychlorinated biphenyls, and bisphenols perturb animal's thyroid endocrine system by mimicking the action of endogenous thyroid hormones (THs), since they share a similar backbone structure of coupled benzene rings with THs. 1-methyl-3-octylimidazolium bromide ([C8mim]Br), a commonly used ionic liquid (IL), has no structural similarity to THs. Whether it interferes with thyroid function and how its mode of action differs from conventional TDCs is largely unknown. Herein, zebrafish embryo-larvae experiments (in vivo), GH3 cell line studies (in vitro), and molecular simulation analyses (in silico) were carried out to explore the effect of [C8mim]Br on thyroid homeostasis and its underlying mechanism. Molecular docking results suggested that [C8mim]+ likely bound to retinoid X receptors (RXRs), which may compromise the formation of TH receptor/RXR heterodimers. This then perturbed the negative regulation of thyroid-stimulating hormone β (tshβ) transcription by T3 in GH3 cell line. The resulting enhancement of tshβ expression further caused hyperthyroidism and developmental toxicity in larval zebrafish. These findings provided a crucial aspect of the ecological risks of ILs, and presented a new insight into the thyroid-disrupting mechanisms for emerging pollutants that do not have structural similarity to THs.
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