Mechanistic aspects the dioxin (aryl hydrocarbon) receptor

  title={Mechanistic aspects the dioxin (aryl hydrocarbon) receptor},
  author={Lorenz Poellinger},
  journal={Food Additives \& Contaminants},
  pages={261 - 266}
  • L. Poellinger
  • Published 1 April 2000
  • Biology, Chemistry
  • Food Additives & Contaminants
The Ah receptor mediates the toxicological responses of 2,3,7,8-TCDD and related compounds. Receptor-deficient animals were shown to be resistant to the toxic effects of dioxin, although there is also evidence for the existence of a receptor-independent pathway for dioxin-induced toxicity. In the cytosol the receptor is present in a non-activated ligand binding conformation. Association with Arnt in the nucleus turns the receptor complex into a ligand activated form. The physiological role of… 

Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology

  • P. Mandal
  • Biology, Chemistry
    Journal of Comparative Physiology B
  • 2005
TCDD induces a broad spectrum of biological responses, including induction of cytochrome P-450 1A1 (CYP1A1), disruption of normal hormone signaling pathways, reproductive and developmental defects, immunotoxicity, liver damage, wasting syndrome, and cancer.

Carcinogenic risks of dioxin: mechanistic considerations.

A ligand for the aryl hydrocarbon receptor isolated from lung

The aryl hydrocarbon receptor (AHR) is a ligand-inducible transcription factor that is best known because it mediates the actions of polycyclic and halogenated aromatic hydrocarbon environmental

The AH receptor of the most dioxin-sensitive species, guinea pig, is highly homologous to the human AH receptor.

There was a distinct correlation across published mammalian species between the number of glutamine residues in the Q-rich subdomain and sensitivity to the acute lethality of TCDD and the closest homolog of the Guinea pig receptor turned out to be the human AHR, which may be relevant for dioxin risk assessment.

Distinct response to dioxin in an arylhydrocarbon receptor (AHR)-humanized mouse

The hAHR knock-in mouse is a humanized model mouse that may better predict the biological effects of bioaccumulative environmental toxicants like TCDD in humans.

The Role of Trace Metals in Cytochrome P4501 Regulation

It is indicated that trace metals diminish the inductive potency of PAHs for these CYPs, and both transcriptional and post-translational mechanisms are involved in the trace metal-mediated down regulation of the CYP1 forms.

The Biological Target Potential of Organometallic Steroids

This work has shown via radioactive labeling that certain organometallic hormone complexes have good targeting ability for nuclear receptors, and introduced the approach using SERMs, SARMs, and so on, which due to their large numbers are only touched on here.

Activation of the dioxin/aryl hydrocarbon receptor (AhR) modulates cell plasticity through a JNK-dependent mechanism

It is shown that dioxin and related pollutants trigger a marked morphological change in epithelial cells that remodel their cytoskeleton to increase interaction with extra cellular matrix while loosening cell–cell contacts.

Identification of novel splice variants of ARNT and ARNT2 in the rat.

Cross-talk of dioxin and estrogen receptor signals through the ubiquitin system




Ah receptor signaling pathways.

The objective is to review the Ah receptor's role in regulation of xenobiotic metabolism and use this model as a framework for understanding the less well-characterized mechanism of dioxin toxicity.

Dioxin binding activities of polymorphic forms of mouse and human arylhydrocarbon receptors.

Modeling receptor-mediated processes with dioxin: implications for pharmacokinetics and risk assessment.

A receptor-mediated physiologically based pharmacokinetic (PB-PK) model for the tissue distribution and enzyme-inducing properties of dioxin is described and the potential role of these models in a biologically motivated risk assessment is discussed.

Loss of teratogenic response to 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) in mice lacking the Ah (dioxin) receptor

There is no direct proof that the AhR is involved in the teratogenic effects of TCDD, but the role of AhR in the regulatory mechanism of xenobiotic‐metabolizing enzymes is investigated.

Aryl-hydrocarbon receptor-deficient mice are resistant to 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced toxicity.

Results suggest that the pathological changes induced by TCDD in the liver and thymus are mediated entirely by the AHR, however, it is important to note that at high doses of T CDD, AHR-deficient mice displayed limited vasculitis and scattered single cell necrosis in their lungs and livers, respectively.

A mechanistic model of effects of dioxin on gene expression in the rat liver.

A mathematical model has been constructed to describe TCDD-mediated alterations in hepatic proteins in the rat and successfully reproduced the observed tissue distribution of T CDD, the concentrations of CYP1A1 and CYP 1A2, and the effects of TCDd on the Ah, estrogen, and EGF receptors over a wide dose range.

Ah receptor, a novel ligand-activated transcription factor.

The aryl hydrocarbon receptor (AhR) is widely distributed in vertebrates and is known to be involved in metabolism of xenobiotics including man-made chemicals, most of which act as a ligand for the

Immune system impairment and hepatic fibrosis in mice lacking the dioxin-binding Ah receptor

The aryl hydrocarbon (Ah) receptor (AHR) mediates many carcinogenic and teratogenic effects of environmentally toxic chemicals such as dioxin and plays an important role in the development of the liver and the immune system.