The effect of aryl hydrocarbon receptor ligands on the expression of AhR, AhRR, ARNT, Hif1alpha, CYP1A1 and NQO1 genes in rat liver.
The aryl hydrocarbon receptor (AhR) mediates a variety of biological responses to ubiquitous environmental pollutants. AhR together with ARNT, AhRR, HIF1alpha represent a novel basic helix-loop-helix/PAS family of transcriptional regulators. Their interplay may affect the xenobiotic response. In this study, the effect of i.p. administration of different AhR ligands on the expression of AhR, AhRR, ARNT, HIF1alpha and CYP1A1 and NAD(P)H: quinone oxidoreductase (NQO1), the enzymes controlled by AhR were examined in Sprague-Dawley rat liver. Quantitative real-time RT-PCR analysis revealed no changes in the mRNA expression of ARNT and HIF1alpha following 3-methylcholanthrene (3-MC), 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or beta-naphthoflavone (BNF) treatment. AhRR expression was affected by TCDD but not by BNF and 3-MC. Expression of AhR mRNA and of the markers of its activation, CYP1A1 and NQO1, was significantly increased by administration of TCDD, 3-MC and, to lower extent, BNF. These results indicate that binding of the ligands to AhR up-regulates the mRNA transcription not only of CYP1A1 and NQO1, but also of AhR itself. The level of AhR induction depends on the potency of xenobiotic metabolizing enzymes inducer.
Brauze
Damian
D
Institute of Human Genetics, Polish Academy of Sciences, ul. Strzeszyńska 32, 60-479 Poznań, Poland. brauzdam@man.poznan.pl
Widerak
Magdalena
M
Cwykiel
Joanna
J
Szyfter
Krzysztof
K
Baer-Dubowska
Wanda
W
D000818:Animals; D051784:Aryl Hydrocarbon Receptor Nuclear Translocator / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D005260:Female; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics*; D008024:Ligands; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008748:Methylcholanthrene / Q000633:toxicity; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D012097:Repressor Proteins / Q000235:genetics*; D019324:beta-Naphthoflavone / Q000633:toxicity
D051784:Aryl Hydrocarbon Receptor Nuclear Translocator; D051792:Basic Helix-Loop-Helix Proteins; D019363:Cytochrome P-450 CYP1A1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008024:Ligands; D008748:Methylcholanthrene; D016660:NAD(P)H Dehydrogenase (Quinone); D000072317:Polychlorinated Dibenzodioxins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D012097:Repressor Proteins; D019324:beta-Naphthoflavone; C497398:ARNT protein, rat; C492161:Ahrr protein, rat; C497444:Hif1a protein, rat; C507703:NQO1 protein, rat