Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Chem Biol Interact
2010 Jan 05;1831:202-11. doi: 10.1016/j.cbi.2009.09.017.
Show Gene links
Show Anatomy links
Responsiveness of a Xenopus laevis cell line to the aryl hydrocarbon receptor ligands 6-formylindolo[3,2-b]carbazole (FICZ) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
???displayArticle.abstract???
The aryl hydrocarbon receptor (AHR) mediates the toxic effects of environmental contaminants, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Frogs are very insensitive to TCDD toxicity, and AHRs from Xenopus laevis (African clawed frog) bind TCDD with >20-fold lower affinity than mouse AHR(b-1). Frog AHRs may nonetheless be highly responsive to structurally distinct compounds, especially putative endogenous ligands. We sought to determine the responsiveness of an X. laevis cell line, XLK-WG, to the candidate endogenous AHR ligand 6-formylindolo[3,2-b]carbazole (FICZ), a tryptophan photoproduct that exhibits high potency in mammalian systems. FICZ readily induced mRNAs for CYP1A6 and CYP1A7. Cells exposed to FICZ for 3h expressed up to 5-fold greater quantities of CYP1A6/7 mRNAs than those exposed for 24h, suggesting FICZ is metabolized following rapid enzyme induction. FICZ appeared more potent than TCDD. Following a 3-h exposure, the EC(50) for CYP1A6 mRNA induction by FICZ was approximately 6nM, while the TCDD response was greater than 174nM. These potencies were lower than those determined for mouse hepatoma cells (Hepa1c1c7; EC(50)= approximately 0.06nM each). The difference in ligand potency between cell lines was confirmed by induction of ethoxyresorufin-O-deethylase (EROD) activity. mRNA from XLK-WG cells treated with 100nM FICZ, 100nM TCDD, or vehicle was also analyzed on expression microarrays. FICZ altered the expression of 105 more transcripts than TCDD, and common targets were altered more dramatically by FICZ. Overall, these studies demonstrate that although FICZ is a less potent CYP1A inducer in frog cells than in mouse cells, the reduction is much less than for TCDD. Relative conservation of the FICZ response in a TCDD-insensitive species suggests its physiological importance as an AHR ligand.
Agostinis,
The Aryl hydrocarbon receptor: an illuminating effector of the UVB response.
2007, Pubmed
Agostinis,
The Aryl hydrocarbon receptor: an illuminating effector of the UVB response.
2007,
Pubmed
Antkiewicz,
Blocking expression of AHR2 and ARNT1 in zebrafish larvae protects against cardiac toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin.
2006,
Pubmed
Bollérot,
Molecular cloning and embryonic expression of the Xenopus Arnt gene.
2001,
Pubmed
,
Xenbase
Ceriani,
Light-dependent sequestration of TIMELESS by CRYPTOCHROME.
1999,
Pubmed
Devary,
NF-kappa B activation by ultraviolet light not dependent on a nuclear signal.
1993,
Pubmed
Diani-Moore,
Sunlight generates multiple tryptophan photoproducts eliciting high efficacy CYP1A induction in chick hepatocytes and in vivo.
2006,
Pubmed
Dougherty,
Analysis of Ah receptor-ARNT and Ah receptor-ARNT2 complexes in vitro and in cell culture.
2008,
Pubmed
Drutel,
Cloning and selective expression in brain and kidney of ARNT2 homologous to the Ah receptor nuclear translocator (ARNT).
1996,
Pubmed
Fritsche,
Lightening up the UV response by identification of the arylhydrocarbon receptor as a cytoplasmatic target for ultraviolet B radiation.
2007,
Pubmed
Fujita,
Molecular cloning and sequence analysis of cDNAs coding for 3-methylcholanthrene-inducible cytochromes P450 in Xenopus laevis liver.
1999,
Pubmed
,
Xenbase
Gu,
The PAS superfamily: sensors of environmental and developmental signals.
2000,
Pubmed
Hankinson,
Genetic and molecular analysis of the Ah receptor and of Cyp1a1 gene expression.
1991,
Pubmed
Hestermann,
Agonist and chemopreventative ligands induce differential transcriptional cofactor recruitment by aryl hydrocarbon receptor.
2003,
Pubmed
Hestermann,
Relative contributions of affinity and intrinsic efficacy to aryl hydrocarbon receptor ligand potency.
2000,
Pubmed
Hirose,
cDNA cloning and tissue-specific expression of a novel basic helix-loop-helix/PAS factor (Arnt2) with close sequence similarity to the aryl hydrocarbon receptor nuclear translocator (Arnt).
1996,
Pubmed
Hughes,
The evolution of functionally novel proteins after gene duplication.
1994,
Pubmed
,
Xenbase
Jönsson,
The tryptophan photoproduct 6-formylindolo[3,2-b]carbazole (FICZ) binds multiple AHRs and induces multiple CYP1 genes via AHR2 in zebrafish.
2009,
Pubmed
Kannan,
Rapid acid treatment of Escherichia coli: transcriptomic response and recovery.
2008,
Pubmed
Kennedy,
Simultaneous measurement of cytochrome P4501A catalytic activity and total protein concentration with a fluorescence plate reader.
1994,
Pubmed
Klein,
Genetic and genomic tools for Xenopus research: The NIH Xenopus initiative.
2002,
Pubmed
,
Xenbase
Lavine,
Aryl hydrocarbon receptors in the frog Xenopus laevis: two AhR1 paralogs exhibit low affinity for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).
2005,
Pubmed
,
Xenbase
Mandal,
Dioxin: a review of its environmental effects and its aryl hydrocarbon receptor biology.
2005,
Pubmed
Martin,
Xgrip109: a gamma tubulin-associated protein with an essential role in gamma tubulin ring complex (gammaTuRC) assembly and centrosome function.
1998,
Pubmed
,
Xenbase
Mukai,
Effects of tryptophan photoproducts in the circadian timing system: searching for a physiological role for aryl hydrocarbon receptor.
2007,
Pubmed
Mukai,
Behavioral rhythmicity of mice lacking AhR and attenuation of light-induced phase shift by 2,3,7,8-tetrachlorodibenzo-p-dioxin.
2008,
Pubmed
Nebert,
Role of the aromatic hydrocarbon receptor and [Ah] gene battery in the oxidative stress response, cell cycle control, and apoptosis.
2000,
Pubmed
Nguyen,
The search for endogenous activators of the aryl hydrocarbon receptor.
2008,
Pubmed
Oberg,
Identification of the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole, in cell culture medium, as a factor that controls the background aryl hydrocarbon receptor activity.
2005,
Pubmed
Okey,
An aryl hydrocarbon receptor odyssey to the shores of toxicology: the Deichmann Lecture, International Congress of Toxicology-XI.
2007,
Pubmed
Powell,
Functional diversity of vertebrate ARNT proteins: identification of ARNT2 as the predominant form of ARNT in the marine teleost, Fundulus heteroclitus.
1999,
Pubmed
Quintana,
Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor.
2008,
Pubmed
Rannug,
Certain photooxidized derivatives of tryptophan bind with very high affinity to the Ah receptor and are likely to be endogenous signal substances.
1987,
Pubmed
Rokaw,
Chronic regulation of transepithelial Na+ transport by the rate of apical Na+ entry.
1996,
Pubmed
,
Xenbase
Rosette,
Ultraviolet light and osmotic stress: activation of the JNK cascade through multiple growth factor and cytokine receptors.
1996,
Pubmed
Rowatt,
ARNT gene multiplicity in amphibians: characterization of ARNT2 from the frog Xenopus laevis.
2003,
Pubmed
,
Xenbase
Schmidt,
Characterization of a murine Ahr null allele: involvement of the Ah receptor in hepatic growth and development.
1996,
Pubmed
Selby,
Functional redundancy of cryptochromes and classical photoreceptors for nonvisual ocular photoreception in mice.
2000,
Pubmed
Shimba,
Crosstalk between the AHR signaling pathway and circadian rhythm.
2009,
Pubmed
Stephan,
Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions.
1972,
Pubmed
Wei,
Regulation of CYP1A1 transcription via the metabolism of the tryptophan-derived 6-formylindolo[3,2-b]carbazole.
2000,
Pubmed
Wei,
Rapid and transient induction of CYP1A1 gene expression in human cells by the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole.
1998,
Pubmed
Whitlock,
Induction of cytochrome P4501A1.
1999,
Pubmed
Wincent,
The suggested physiologic aryl hydrocarbon receptor activator and cytochrome P4501 substrate 6-formylindolo[3,2-b]carbazole is present in humans.
2009,
Pubmed
