The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver
-
- Karl Walter Bock
- Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Wilhelmstrasse 56, D-72074 Tübingen, Germany
-
- Christoph Köhle
- Department of Toxicology, Institute of Experimental and Clinical Pharmacology and Toxicology, University of Tübingen, Wilhelmstrasse 56, D-72074 Tübingen, Germany
説明
<jats:title>Abstract</jats:title> <jats:p>The mammalian Ah receptor (AhR) is a ligand-activated transcription factor with multiple functions in adaptive metabolism, development and dioxin toxicity in a variety of organs and cell systems. Phenotypes observed following sustained activation by dioxin or in AhR-null mice suggest organ-dependent physiological functions. These functions are probably deregulated following exposure to dioxin. We focus on skin and liver to facilitate discussion of mechanisms linking phenotypes and AhR-modulated genotypes. After a brief summary of currently discussed AhR ligand candidates, two groups of direct AhR target genes/proteins and associated functions are highlighted: (i) xenobiotic-metabolizing enzymes which are also involved in homeostasis of endogenous ligands and (ii) proteins controlling cell proliferation/apoptosis, differentiation and inflammation. Homeostatic feedback loops might not only include CYP1A1 but also Phase II enzymes such as UGT1A1 which controls the antioxidant AhR ligand bilirubin. The AhR is involved in extensive crosstalk with other transcription factors and multiple signaling pathways. Efforts elucidating the pathway toward identification of physiological functions of the AhR remain challenging and promising.</jats:p>
収録刊行物
-
- bchm
-
bchm 390 (12), 1225-1235, 2009-09-13
Walter de Gruyter GmbH
