Abstract

Activation of aryl hydrocarbon receptor (AHR) by xenobiotic toxic chemicals such as 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin regulates a variety of cellular processes including embryogenesis, tumorigenesis and inflammation. However, the identity of endogenous AHR ligands remains elusive. A potential AHR ligand, compound X, was identified from zebrafish embryos using previous developed cell free bioassay for dioxin‐like compounds. In this study, we aim to investigate the effect of compound X in AHR activation and further explore its physiological effects. Compound X induces AHR translocation into nucleus and upregulates downstream cytochrome P450 1A1 (CYP1A1) in vitro. It also promotes neuronal differentiation in neuroblastoma (NB) cells, which is consistent with our previous studies that overexpression of AHR leads to NB cells differentiation. Furthermore, compound X enhances zCyp1a, myelin‐associated myelin basic protein (zMbp) and SRY (sex determining region Y)‐box 10 (zSox10) expression and improves the mobility of zebrafish larvae via Ahr2 pathway. Therefore, our results suggest that compound X is an endogenous AHR ligand, and plays a critical role during neural differentiation.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

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