Re: IBD & Dioxins Link?

> > salicylamide is an antagonist of the aryl hydrocarbon ...
>
> Black tea theaflavins suppress dioxin-induced transformation
> of the aryl hydrocarbon receptor.

Epigallocatechin gallate inhibits aryl hydrocarbon receptor gene
transcription through an indirect mechanism involving binding to a 90
kDa heat shock protein.
The aryl hydrocarbon receptor (AhR) is a ligand-activated
transcription factor known to mediate the toxic effects of numerous
environmental contaminants, including the polycyclic aromatic
hydrocarbons (PAHs). Historically, binding of PAHs to the AhR and the
events leading to the generation of DNA adducts have been associated
with chemical carcinogenesis. Previous investigations have implicated
green tea (GT) as affording protection against PAH-induced cancers in
animal models. Investigations in our laboratory have demonstrated that
the GT polyphenol epigallocatechin gallate (EGCG) is capable of
antagonizing AhR-mediated gene transcription, implicating inhibition
of AhR signaling as a potential chemopreventive mechanism. This line
of investigation was directed at elucidating the molecular mechanism
of this antagonism. Competitive binding assays strongly suggest that
EGCG does not bind to the AhR ligand binding site, indicating this
compound functions through a mechanism unlike that of typical AhR
antagonists. Affinity chromatography experiments implicate an indirect
mechanism of action involving direct binding of EGCG to the AhR
chaperone protein, hsp90. This induces an AhR conformation capable of
nuclear localization but incapable of binding DNA. These altered
signaling events correlate with the formation of a complex with
sedimentation characteristics different from those of the latent or
ligand-activated AhR. These data implicate a model in which EGCG
inhibits release of hsp90 from the AhR, stabilizing the complex in an
intermediary state associated with XAP2. This is the first time EGCG
has been demonstrated to directly bind hsp90 and the first indication
that GT may exert its chemopreventive effects through an interaction
with the common chaperone hsp90. PMID: 15794642