Suppression ofCYP1A1Transcription by H2O2Is Mediated by Xenobiotic-Response Element

Xu, Chuanli; Pasco, David S.

doi:10.1006/abbi.1998.0770

Cited by 18 publications

(12 citation statements)

References 44 publications

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“…Interestingly, studies conducted with hepatoma cells suggest that oxidation of NF1 protein binding to a proximal NF1 site in the CYP1A1 promoter, which acts in synergy with XRE regions, constitutes the basis of suppression of CYP1A induction by ROS: the NF1/CTF trans-activating domain was repressed by oxidative stress, mediated by a critical cysteine . On the other hand, a different study indicates that the H 2 O 2 -dependent suppression of CYP1A1 induction is linked to the potential of the XREs to confer transcriptional activation by aromatic hydrocarbons (Xu and Pasco, 1998). Further examples of redox-sensitive regulation have been provided for members of the nuclear receptor superfamily .…”

Section: Discussionmentioning

confidence: 99%

Repression of Phenobarbital-Dependent CYP2B1 mRNA Induction by Reactive Oxygen Species in Primary Rat Hepatocyte Cultures

et al. 2001

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Xenobiotic-metabolizing cytochrome P-450 (P-450) enzymes not only play a pivotal role in elimination of foreign compounds but also contribute to generation of toxic intermediates, including reactive oxygen species, that may elicit cellular damage if produced excessively. Expression of several xenobiotic-metabolizing P-450 enzymes is induced by phenobarbital (PB). Pronounced induction is observed for the rat CYP2B1 isoform. A primary rat hepatocyte culture system was used to investigate whether reactive oxygen species might modulate PBdependent CYP2B1 induction. In cells cultivated for 3 days with 1.5 mM PB, substantial CYP2B1 mRNA induction was observed (100%). Addition of H 2 O 2 or of the catalase inhibitor 3-amino-1,2,4-triazole (AT) to the medium repressed induction to approximately 30% (at 1 mM H 2 O 2 and 2 mM AT, respectively). Accordingly, treatment of hepatocytes with PB and the glutathione precursor N-acetylcysteine (NAC) led to enhanced PB-dependent induction (to over 1000% at 10 mM NAC). In primary hepatocyte cultures transfected with a CYP2B1 promoter-luciferase construct containing approximately 2.7 kilobase pairs of the native CYP2B1 promoter sequence, PBdependent reporter gene activation was repressed by AT and stimulated by N-acetylcysteine. Furthermore, a 263-base pair CYP2B1 promoter fragment encompassing the phenobarbitalresponsive enhancer module conferred suppression of PBdependent luciferase expression by AT and activation by NAC in a heterologous SV40-promoter construct. In summary, these data demonstrate a regulatory mechanism that is dependent on the cellular redox status, which modulates CYP2B1 mRNA induction by PB on the transcriptional level, thus representing a feedback mechanism preventing further P-450 -dependent production of reactive oxygen intermediates under oxidative stress.

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Section: Discussionmentioning

confidence: 99%

Repression of Phenobarbital-Dependent CYP2B1 mRNA Induction by Reactive Oxygen Species in Primary Rat Hepatocyte Cultures

et al. 2001

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“…The regulation of the AhR [which binds to so-called xenobioticresponsive element (XRE) DNA sequences] by oxidative stress is unclear. Its DNA binding is not affected by oxidative stress [145]. Transfection studies on the induction of the CYP1A1 gene showed that the response mediated by XRE sequences seemed to be unaffected by H # O # concentrations that strongly repress NFI [93].…”

Section: Transcription Factors Containing a Helix-loop-helix (Hlh) Motifmentioning

confidence: 97%

“…Transfection studies on the induction of the CYP1A1 gene showed that the response mediated by XRE sequences seemed to be unaffected by H # O # concentrations that strongly repress NFI [93]. However, another study showed that higher (millimolar) H # O # concentrations could repress reporter genes driven by XRE sequences [145]. Thus the AhR may be sensitive to strong oxidation conditions but remain unaffected by moderate ROS concentrations.…”

Section: Transcription Factors Containing a Helix-loop-helix (Hlh) Motifmentioning

confidence: 99%

Repression of gene expression by oxidative stress

Morel

Barouki

1999

Biochemical Journal

330

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Gene expression is modulated by both physiological signals (hormones, cytokines, etc.) and environmental stimuli (physical parameters, xenobiotics, etc.). Oxidative stress appears to be a key pleiotropic modulator which may be involved in either pathway. Indeed, reactive oxygen species (ROS) have been described as second messengers for several growth factors and cytokines, but have also been shown to rise following cellular insults such as xenobiotic metabolism or enzymic deficiency. Extensive studies on the induction of stress-response genes by oxidative stress have been reported. In contrast, owing to the historical focus on gene induction, less attention has been paid to gene repression by ROS. However, a growing number of studies have shown that moderate (i.e. non-cytotoxic) oxidative stress specifically down-regulates the expression of various genes. In this review, we describe the alteration of several physiological functions resulting from oxidative-stress-mediated inhibition of gene transcription. We will then focus on the repressive oxidative modulation of various transcription factors elicited by ROS.

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“…Tandem DREs have a cooperative effect on gene expression (Rushmore & Pickett 1990; Xu & Pasco 1998). To evaluate the distribution of tandemly arranged DREs, we defined the combination of two DREs as a ‘pair’.…”

Section: Methodsmentioning

confidence: 99%

Genome‐wide screening of dioxin‐responsive genes in fetal brain: bioinformatic and experimental approaches

Fujita

Samejima

Kitagawa

et al. 2006

Congenital Anomalies

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Many of the effects of dioxins, which are potent environmental pollutants and teratogens, are mediated through the aryl hydrocarbon receptor, also known as the dioxin receptor. The purpose of the present study was to characterize dioxin-responsive genes in a comprehensive manner using two complementary approaches: bioinformatic analysis and microarray analysis. First, we characterized the overall distribution of the cis-regulatory element for the dioxin-responsive element sequence (DRE) 'gcgtg' within putative promoter regions. We assembled the upstream sequences 10 kb from the transcription start site and evaluated their location and frequency in the human and mouse genomes. Second, we characterized the expression profile of mouse embryonic day 12 fetal brain exposed to 2,3,7,8-tetrarchlorodibenzo-p-dioxin. The distributions of 26,680 DREs among 2,843 human genes and 98,711 DREs among 18,541 mouse genes were examined. In both species, the DREs tended to be located close to the transcription start site. Forty genes exhibited significant induction or repression following dioxin exposure in fetal mice. The set of genes exhibited a strong functional coherence, with statistically significant enrichment in organogenesis and the DNA-dependent regulation of transcription, according to Gene Ontology annotations. In both humans and mice, DREs were preferentially distributed close to transcription start sites. Evolutionary conservation of this unique DRE distribution pattern suggests that DREs may be involved in transcriptional regulation. In mice, prenatal dioxin exposure altered the expression of 10 transcription factors, many of which have been documented to play a role in organogenesis. These genes may represent potential mediators of dioxin's effects in fetal tissues.

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Suppression ofCYP1A1Transcription by H2O2Is Mediated by Xenobiotic-Response Element

Cited by 18 publications

References 44 publications

Repression of Phenobarbital-Dependent CYP2B1 mRNA Induction by Reactive Oxygen Species in Primary Rat Hepatocyte Cultures

Repression of Phenobarbital-Dependent CYP2B1 mRNA Induction by Reactive Oxygen Species in Primary Rat Hepatocyte Cultures

Repression of gene expression by oxidative stress

Genome‐wide screening of dioxin‐responsive genes in fetal brain: bioinformatic and experimental approaches

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