Regulatory effects of carotenoids on Aryl hydrocarbon receptor (AhR) gene battery

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[Introduction] In our previous work, positive correlations between CYP1A- dependent activities, protein expression and β-carotene (BC) accumulation in the ungulates were observed, however these cross-talks were poorly understood. Additionally, the regulatory effects of carotenoids on xenobiotics metabolizing enzymes (XMEs) had received little attention. Thus, the aim of the current study is to deeply investigate the constitutive response of AhR gene battery to the exposure to BC under various doses in the human hepatoma cell line (HEPG2) cells. Moreover, the possible regulatory mechanisms of these cross-talks between AhR and BC will be declared. [Materials and Methods] HEPG2 cell lines were treated with different concentrations of BC (0-10 µM) for 12-24h. The mRNA expression for phase I (CYP1A1 and 1A2), Phase II (UGT1A6 and NQO1) enzymes and AhR were examined using Real-Time PCR. Protein expression of AhR was investigated using western blotting. Rat H4IIE cells were transfected with h-XRE luciferase reporter plasmid and exposed to BC for 24h and dual- luciferase reporter assay was performed. [Results and Discussion] BC differentially modulated XMEs (Phase I and II enzymes) expression in dose-dependent fashion. In parallel, BC induced AhR mRNA, protein expression and luciferase activity. Thus, β-carotene differentially modulated AhR gene battery.
日本毒性学会の論文