AH receptor antagonist inhibits constitutive CYP1A1 and CYP1B1 expression in rat BP8 cells

Roblin, Steven; Okey, Allan B.; Harper, Patricia A.

doi:10.1016/j.bbrc.2004.03.016

Cited by 19 publications

(9 citation statements)

References 46 publications

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“…Our results showed that TCDD-induced CYP1A1 expression was partially reversed by resveratrol in a dose-dependent manner. The incomplete reversal of CYP1A1 expression by resveratrol may be due to the fact that AhR is not the only regulator of CYP1A1 transcription [38,39] . Taken together, these results suggest that the AhR signal pathway could be activated in GC cells and that abnormal activation of the AhR signal pathway may be involved in gastric carcinogenesis.…”

Section: Discussionmentioning

confidence: 99%

Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

Peng

Chen²,

Mao³

et al. 2009

WJG

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Section: Discussionmentioning

confidence: 99%

Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

Peng

Chen²,

Mao³

et al. 2009

WJG

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“…Thus, it is not surprising that numerous studies have suggested that these pathways may exhibit crosstalk in their regulation of gene expression [13][14][15][16]. However, essentially all previous studies have focused on the interaction of hypoxia and AHR signaling when the AHR is activated by exogenous ligands, despite the fact that AHR regulates constitutive CYP1A1 expression in the absence of exogenous ligands [17,18] and hypoxia alone can induce or repress CYP1A1 expression depending on the model studied [19,20].…”

mentioning

confidence: 92%

Crosstalk Between the Aryl Hydrocarbon Receptor and Hypoxia on the Constitutive Expression of Cytochrome P4501A1 mRNA

Zhang

Walker

2007

Cardiovasc Toxicol

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Endothelial cells are a target of halogenated aromatic hydrocarbon toxicity following aryl hydrocarbon receptor (AHR) activation. Further, evidence suggests that AHR has a physiological function in endothelial cells in the absence of exogenous ligands. Understanding these "normal" functions of AHR may help to reveal the mechanisms that contribute to the toxicity of xenobiotic ligands. Thus, this study focused on the crosstalk between hypoxia and AHR in the absence of exogenous ligands. Constitutive CYP1A1 mRNA was measured by real time PCR in human pulmonary microvascular endothelial cells exposed to hypoxia (1 or 2.5% O2), 25 nM AHR siRNA, 25 nM hypoxia-inducible factor (HIF)-2alpha siRNA, or their combinations. Hypoxia significantly induced known hypoxia-regulated genes, and this induction was highly attenuated by HIF-2alpha siRNA, suggesting that HIF-2alpha is a primary mediator of hypoxic responses in these cells. Hypoxia also significantly reduced CYP1A1 mRNA and this reduction was also attenuated by HIF-2alpha siRNA. As expected, AHR siRNA significantly reduced constitutive CYP1A1 mRNA. While the combination of hypoxia plus AHR siRNA reduced CYP1A1 mRNA more than either treatment alone, the reduction was less than additive, suggesting that hypoxia and AHR deficiency may share a common pathway in reducing CYP1A1 expression. Finally, hypoxia significantly reduced AHR mRNA and this reduction was completely prevented by HIF-2alpha siRNA. In conclusion, constitutive CYP1A1 mRNA expression is dependent on AHR and is reduced by hypoxia via a HIF-2alpha-dependent mechanism, which may be mediated by a HIF-2alpha-dependent reduction of AHR expression.

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“…Band intensity was quantitated using ImageQuant software (Amersham Biosciences Inc.). Primer sequences used were: CYP1A1 forward, 5Ј-GACCTGAATGAGAAGTTCTACAGC-3Ј; reverse, 5Ј-CGGAAGGTCTC-CAGGATGAAG-3Ј; and ␤-actin forward, 5Ј-CTACAATGAGCTGCGTGTGG-3Ј; reverse, 5Ј-TAGCTCTTCTCCAGGGAGGA-3Ј, as described previously (Li et al, 1998;Roblin et al, 2004).…”

mentioning

confidence: 99%

tert-BUTYLHYDROQUINONE IS A NOVEL ARYL HYDROCARBON RECEPTOR LIGAND

Gharavi¹,

El‐Kadi²

2004

Drug Metab Dispos

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ABSTRACT:In contrast to the beneficial effects of tert-butylhydroquinone (tBHQ) as a food antioxidant, a number of studies have shown that chronic exposure to tBHQ may induce carcinogenicity. Therefore, we examined the ability of tBHQ to induce the cytochrome P450 1a1 (Cyp1a1), an enzyme known to play an important role in the chemical activation of xenobiotics to carcinogenic derivatives. A significant concentration-dependent increase in Cyp1a1 mRNA, protein, and activity occurred after treatment of murine hepatoma Hepa 1c1c7 cells with tBHQ. The increase in mRNA was apparent 3 h after treatment. The RNA polymerase inhibitor, actinomycin D, completely blocked the Cyp1a1 induction by tBHQ, indicating a requirement of de novo RNA synthesis through transcriptional activation. The protein synthesis inhibitor cycloheximide superinduced the tBHQ-mediated induction of Cyp1a1 mRNA and completely prevented the increase in Cyp1a1 activity, indicating that the induction of enzyme activity by tBHQ is dependent on de novo protein synthesis. In addition, the aryl hydrocarbon receptor (AHR) antagonist, resveratrol, inhibited the increase in Cyp1a1 activity by tBHQ. Gel electrophoretic mobility shift assays showed that tBHQ causes activation or transformation of the AHR in nuclear extracts, indicating that AHR-dependent mechanisms contributed to the Cyp1a1 induction. Similar to murine Hepa 1c1c7 cells, tBHQ caused a concentration-dependent increase in CYP1A1 at the mRNA and activity levels in human HepG2 cells. This is the first demonstration that the phenolic antioxidant, tBHQ, can directly induce Cyp1a1 gene expression in an AHR-dependent manner and may represent a novel mechanism by which tBHQ promotes carcinogenicity.

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AH receptor antagonist inhibits constitutive CYP1A1 and CYP1B1 expression in rat BP8 cells

Cited by 19 publications

References 46 publications

Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

Crosstalk Between the Aryl Hydrocarbon Receptor and Hypoxia on the Constitutive Expression of Cytochrome P4501A1 mRNA

tert-BUTYLHYDROQUINONE IS A NOVEL ARYL HYDROCARBON RECEPTOR LIGAND

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