Loss of hepatic aryl hydrocarbon receptor protein in adrenalectomized rats does not involve altered levels of the receptor’s cytoplasmic chaperones

The aryl hydrocarbon receptor (AHR) plays physiological roles and mediates adaptive and toxic responses to environmental pollutants. Adrenalectomized rats display decreased hepatic AHR protein levels, with no change in mRNA, and selectively impaired induction of cytochrome P450 1B1. This is similar to reported phenotypes for mice with hepatocyte-specific conditional deletion of AHR-interacting protein (AIP), a chaperone protein of the cytoplasmic AHR complex. In this study, we demonstrated that adrenalectomy (ADX) and acute dexamethasone (DEX) treatment do not alter hepatic AIP mRNA or protein levels. Also, hepatic protein levels of the 90 kDa heat shock protein and p23 were not altered by ADX or acute DEX treatment. These results suggest that the loss of rat hepatic AHR protein following ADX cannot be explained by changes in the levels of the receptor’s cytoplasmic chaperone proteins.

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Expression, Localization, and Activity of the Aryl Hydrocarbon Receptor in the Human Placenta

International Journal of Molecular Sciences ◽

10.3390/ijms19123762 ◽

2018 ◽

Vol 19 (12) ◽

pp. 3762 ◽

Cited By ~ 8

Author(s):

Anaïs Wakx ◽

Margaux Nedder ◽

Céline Tomkiewicz-Raulet ◽

Jessica Dalmasso ◽

Audrey Chissey ◽

...

Keyword(s):

Aryl Hydrocarbon Receptor ◽

Human Placenta ◽

Target Genes ◽

Environmental Pollutants ◽

Cell Fractionation ◽

Protein Levels ◽

Aryl Hydrocarbon ◽

Epithelial Barriers ◽

Expression And Activity

The human placenta is an organ between the blood of the mother and the fetus, which is essential for fetal development. It also plays a role as a selective barrier against environmental pollutants that may bypass epithelial barriers and reach the placenta, with implications for the outcome of pregnancy. The aryl hydrocarbon receptor (AhR) is one of the most important environmental-sensor transcription factors and mediates the metabolism of a wide variety of xenobiotics. Nevertheless, the identification of dietary and endogenous ligands of AhR suggest that it may also fulfil physiological functions with which pollutants may interfere. Placental AhR expression and activity is largely unknown. We established the cartography of AhR expression at transcript and protein levels, its cellular distribution, and its transcriptional activity toward the expression of its main target genes. We studied the profile of AhR expression and activity during different pregnancy periods, during trophoblasts differentiation in vitro, and in a trophoblast cell line. Using diverse methods, such as cell fractionation and immunofluorescence microscopy, we found a constitutive nuclear localization of AhR in every placental model, in the absence of any voluntarily-added exogenous activator. Our data suggest an intrinsic activation of AhR due to the presence of endogenous placental ligands.

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