Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator
Quinone-mediated induction of cytochrome P450 1A1 in HepG2 cells through increased interaction of aryl hydrocarbon receptor with aryl hydrocarbon receptor nuclear translocator
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DOI：
10.2131/jts.41.775
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发表时间：
2016-12-01
影响因子：
2
通讯作者：
Kumagai, Yoshito
中科院分区：
文献类型：
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作者：
Abiko, Yumi;Lin, Fang-Yu;Kumagai, Yoshito
虽然长期以来一直认为苯和萘不能激活芳烃受体（AhR），因为它们是不良配体，但我们最近报道这些醌型代谢物上调Hepalcic 7细胞中的细胞色素P450 1A 1（CYP 1A 1）（Abiko et al.，2015）。在目前的研究中，AhR激活，测量与生物发光为基础的无细胞测定，诱导1，2-萘醌（1，2-NQ），萘的代谢产物。与此一致，1，4-苯醌（1，4-BQ），叔丁基-1，4-BQ，1，4-NQ，以及1，2-NQ，所有亲电子单环和双环醌，上调HepG 2细胞中的CYP 1A 1 mRNA和蛋白质，而它们的母体芳烃几乎没有影响。此外，免疫荧光分析证实，这些醌类增强AhR向细胞核的易位。
While it has long been believed that benzenes and naphthalenes are unable to activate the aryl hydrocarbon receptor (AhR) because they are poor ligands, we recently reported that these quinoid metabolites upregulated cytochrome P450 1A1 (CYP1A1) in Hepalcic7 cells (Abiko et al., 2015). In the current study, AhR activation, measured with a bioluminescence-based cell free assay, was induced by 1,2-naphthoquinone (1,2-NQ), a metabolite of naphthalene. Consistent with this, 1,4-benzoquinone (1,4-BQ), tert-butyl-1,4-BQ, and 1,4-NQ, as well as 1,2-NQ, all electrophilic mono- and bi-cyclic quinones, upregulated CYP1A1 mRNA and protein in HepG2 cells, whereas their parent aromatic hydrocarbons had little effect. Furthermore, immunofluorescence analysis confirmed that these quinones enhanced translocation of AhR to the nucleus.