scholarly journals Non-hypoxic transcriptional activation of the aryl hydrocarbon receptor nuclear translocator in concert with a novel hypoxia-inducible factor-1alpha isoform

2004 ◽  
Vol 32 (18) ◽  
pp. 5499-5511 ◽  
Author(s):  
K.-H. Lee
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Transcriptional Activation ◽  
Hypoxia Inducible Factor ◽  
Aryl Hydrocarbon

Role of aryl hydrocarbon receptor in modulation of the expression of the hypoxia marker carbonic anhydrase IX

2009 ◽  
Vol 419 (2) ◽  
pp. 419-425 ◽  
Author(s):  
Martina Takacova ◽  
Tereza Holotnakova ◽  
Jan Vondracek ◽  
Miroslav Machala ◽  
Katerina Pencikova ◽  
...  
Keyword(s):  
Carbonic Anhydrase ◽  
Aryl Hydrocarbon Receptor ◽  
Transcriptional Activation ◽  
Hypoxia Inducible Factor ◽  
Carbonic Anhydrase Ix ◽  
Independent Manner ◽  
Hypoxic Induction ◽  
Aryl Hydrocarbon ◽  
Ca Ix ◽  
Tcdd Treatment

Tumour-associated expression of CA IX (carbonic anhydrase IX) is to a major extent regulated by HIF-1 (hypoxia-inducible factor-1) which is important for transcriptional activation and consists of the oxygen-regulated subunit HIF-1α and the partner factor ARNT [AhR (aryl hydrocarbon receptor) nuclear translocator]. We have previously observed that HIF-1α competes with the AhR for interaction with ARNT under conditions when both conditionally regulated factors are activated. We have therefore investigated whether TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin)-induced activation of the AhR pathway might interfere with CA IX expression. The results from the present study suggest that TCDD treatment reduces hypoxic induction of both CA IX mRNA and protein expression. Moreover, the transcriptional activity of the CA9 promoter was significantly reduced by expression of CAAhR (constitutively active AhR), which activates transcription in a ligand-independent manner. Finally, we found that ARNT is critical for both hypoxic induction and the TCDD-mediated inhibition of CA9 expression.

scholarly journals Activation of aryl hydrocarbon receptor mediates suppression of hypoxia-inducible factor-dependent erythropoietin expression by indoxyl sulfate

2016 ◽  
Vol 310 (2) ◽  
pp. C142-C150 ◽  
Author(s):  
Hirobumi Asai ◽  
Junya Hirata ◽  
Ayumi Hirano ◽  
Kazuya Hirai ◽  
Sayaka Seki ◽  
...  
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Mrna Expression ◽  
Transcriptional Activation ◽  
Hypoxia Inducible Factor ◽  
Indoxyl Sulfate ◽  
Renal Anemia ◽  
Nuclear Accumulation ◽  
Blood Levels ◽  
Uremic Toxin ◽  
Aryl Hydrocarbon

Indoxyl sulfate (IS) is a representative uremic toxin that accumulates in the blood of patients with chronic kidney disease (CKD). In addition to the involvement in the progression of CKD, a recent report indicates that IS suppresses hypoxia-inducible factor (HIF)-dependent erythropoietin (EPO) production, suggesting that IS may also contribute to the progression of renal anemia. In this report, we provide evidence that aryl hydrocarbon receptor (AhR) mediates IS-induced suppression of HIF activation and subsequent EPO production. In HepG2 cells, IS at concentrations similar to the blood levels in CKD patients suppressed hypoxia- or cobalt chloride-induced EPO mRNA expression and transcriptional activation of HIF. IS also induced AhR activation, and AhR blockade resulted in abolishment of IS-induced suppression of HIF activation. The HIF transcription factor is a heterodimeric complex composed of HIF-α subunits (HIF-1α and HIF-2α) and AhR nuclear translocator (ARNT). IS suppressed nuclear accumulation of the HIF-α-ARNT complex accompanied by an increase of the AhR-ARNT complex in the nucleus, implying the involvement of interactions among AhR, HIF-α, and ARNT in the suppression mechanism. In rats, oral administration of indole, a metabolic precursor of IS, inhibited bleeding-induced elevation of renal EPO mRNA expression and plasma EPO concentration and strongly induced AhR activation in the liver and renal cortex tissues. Collectively, this study is the first to elucidate the detailed mechanism by which AhR plays an indispensable role in the suppression of HIF activation by IS. Hence, IS-induced activation of AhR may be a potential therapeutic target for treating renal anemia.

scholarly journals Role of Mediator in Transcriptional Activation by the Aryl Hydrocarbon Receptor

2004 ◽  
Vol 279 (14) ◽  
pp. 13593-13600 ◽  
Author(s):  
Song Wang ◽  
Kai Ge ◽  
Robert G. Roeder ◽  
Oliver Hankinson
Keyword(s):  
Aryl Hydrocarbon Receptor ◽  
Transcriptional Activation ◽  
Aryl Hydrocarbon

scholarly journals Aryl Hydrocarbon Receptor-Mediated Transcription: Ligand-Dependent Recruitment of Estrogen Receptor α to 2,3,7,8-Tetrachlorodibenzo- p-Dioxin-Responsive Promoters

2005 ◽  
Vol 25 (13) ◽  
pp. 5317-5328 ◽  
Author(s):  
Jason Matthews ◽  
Björn Wihlén ◽  
Jane Thomsen ◽  
Jan-Åke Gustafsson
Keyword(s):  
Estrogen Receptor ◽  
Aryl Hydrocarbon Receptor ◽  
Rna Polymerase Ii ◽  
Transcriptional Activation ◽  
Time Course ◽  
Estrogen Receptor Α ◽  
Time Dependent ◽  
Promoter Regions ◽  
Aryl Hydrocarbon ◽  
H3 Acetylation

ABSTRACT Using chromatin immunoprecipitation assays, we studied the 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-mediated recruitment of the aryl hydrocarbon receptor (AhR) and several coregulators to the CYP1A1 promoter. AhR displayed a time-dependent recruitment, reaching a peak at 75 min and maintaining promoter occupancy for the remainder of the time course. Recruitment of AhR was followed by TIF2/SRC2, which preceded CBP, histone H3 acetylation, and RNA polymerase II (RNAPII). Simultaneous recruitment to the enhancer and the TATA box region suggests the formation of a large multiprotein complex bridging the two promoter regions. Interestingly, estrogen receptor α (ERα) displayed a TCDD- and time-dependent recruitment to the CYP1A1 promoter, which was increased by cotreatment with estradiol. Transfection in HuH7 human liver cells confirmed previously reported ERα enhancement of AhR activity. In contrast, TCDD did not induce the recruitment of ERα to the estrogen-responsive pS2 promoter, and after 120 min of cotreatment with estradiol, ERα is still present on the CYP1A1 promoter but no longer at pS2. RNA interference studies with T47D cells support a role for ERα in TCDD-dependent CYP1A1 expression. Our data suggest that ERα acts as a coregulator of AhR-mediated transcriptional activation and that the recruitment of ERα by AhR represents a novel mechanism AhR-ERα cross talk.

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