The mammalian aryl hydrocarbon (Ah) receptor: from mediator of dioxin toxicity toward physiological functions in skin and liver

被引:69
作者
Bock, Karl Walter [1 ]
Koehle, Christoph [1 ]
机构
[1] Univ Tubingen, Dept Toxicol, Inst Expt & Clin Pharmacol & Toxicol, D-72074 Tubingen, Germany
关键词
Ah receptor ligands; Ah receptor target genes; apoptosis; cell differentiation; cell proliferation; inflammation; SIGNAL-TRANSDUCTION PATHWAY; DRUG-METABOLIZING-ENZYMES; IN-UTERO EXPOSURE; RAT-LIVER; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN TCDD; CONSTITUTIVE EXPRESSION; RETINOID ACCUMULATION; COORDINATE REGULATION; TRANSCRIPTION FACTOR; GENE-EXPRESSION;
D O I
10.1515/BC.2009.138
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1225 / 1235
页数:11
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