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

Abstract:

: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-methylcholanthrene to the AhR. In mouse hepatoma Hepa-1c1c7 cells, indigoids, especially indirubin, suppressed the transformation and expression of CYP1A1 by inhibiting the translocation of AhR into the nucleus. When orally administered to mice at 10mg/kg BW/day for three successive days, indigoids did not induce AhR transformation and expression of the CYP1A 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.

journal_name

Arch Biochem Biophys

authors

Nishiumi S,Yamamoto N,Kodoi R,Fukuda I,Yoshida K,Ashida H

doi

10.1016/j.abb.2007.11.021

subject

Has Abstract

pub_date

2008-02-15 00:00:00

pages

187-99

issue

2

eissn

0003-9861

issn

1096-0384

pii

S0003-9861(07)00577-2

journal_volume

470

pub_type

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