Antagonistic and agonistic effects of indigoids on the transformation of an aryl hydrocarbon receptor

被引：32

作者：

Nishiumi, Shin ^{[1
]}

Yamamoto, Norio ^{[2
]}

Kodoi, Rie ^{[1
]}

Fukuda, Itsuko ^{[3
]}

Yoshida, Ken-Ichi ^{[1
]}

Ashida, Hitoshi ^{[1
,3
]}

机构：

[1] Kobe Univ, Grad Sch Agr Sci, Dept Agrobiosci, Nada Ku, Kobe, Hyogo 6578501, Japan

[2] House Wellness Foods Co, Dept Res & Dev, Res Sect, Itami, Hyogo 6640011, Japan

[3] Kobe Univ, Grad Sch Agr Sci, Res Ctr Food Safety & Security, Kobe, Hyogo 6578501, Japan

来源：

ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS | 2008年 / 470卷 / 02期

基金：

日本学术振兴会;

关键词：

aryl hydrocarbon receptor; indigoid; indirubin; indigo; TCDD; transformation; CYPIAI; quinone reductase;

D O I：

10.1016/j.abb.2007.11.021

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Halogenated and polycyclic aromatic hydrocarbons, exogenous ligands of the aryl hydrocarbon receptor (AhR), cause various toxicological effects through the transformation of the AhR. In this study, we investigated the antagonistic effects of indigoids on the transformation in addition to their agonistic ones. In a cell-free system, indigoids induced the transformation dose-dependently, but suppressed the transformation induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin and the binding of 3-methyleholanthrene to the AhR. In mouse hepatoma Hepa-1clc7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYPIAI by inhibiting the translocation of AhR into the nucleus. When orally administered to mice at 10 mg/kg BW/day for three successive days, indigoids did not induce AhR transformation and expression of the CYPIA subfamily in the liver, while indirubin and indigo upregulated quinone reductase activity. These results indicate that indigoids are able to bind to the AhR as ligands and exhibit antagonistic effects at lower concentrations in mammalian cells. (c) 2007 Elsevier Inc. All rights reserved.

引用

页码：187 / 199

页数：13

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