Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5

Ashino, Takashi; Ohkubo-Morita, Haruyo; Yamamoto, Masayuki; Yoshida, Takemi; Numazawa, Satoshi

doi:10.1016/j.redox.2013.12.025

Cited by 26 publications

(24 citation statements)

References 22 publications

(17 reference statements)

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“…These genes are regulated in an age- and tissue-specific fashion by PEITC with different modes of actions: Following PEITC treatment, CAR appears to be the dominant regulator in CYP2B10 induction, whereas activation of both CAR and Nrf2 is associated with UGT1A1 induction. In line with these results is the evidence that the PBREM but not the ARE region has been identified in the Cyp2b10 promoter45, although it has recently been suggested that Nrf2 is involved in phorone induction of Cyp2b10 46. In contrast, both response elements have been proven to be functional and located adjacent to each other within UGT1A1 promoter sequences30.…”

Section: Discussionmentioning

confidence: 71%

Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress

Yoda

Paszek

Konopnicki

et al. 2017

Sci Rep

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Isothiocyanates, such as phenethyl isothiocyanate (PEITC), are formed following the consumption of cruciferous vegetables and generate reactive oxygen species (ROS) that lead to the induction of cytoprotective genes such as the UDP-glucuronosyltransferases (UGTs). The induction of ROS activates the Nrf2-Keap 1 pathway leading to the induction of genes through antioxidant response elements (AREs). UGT1A1, the sole enzyme responsible for the metabolism of bilirubin, can be induced following activation of Nrf2. When neonatal humanized UGT1 (hUGT1) mice, which exhibit severe levels of total serum bilirubin (TSB) because of a developmental delay in expression of the UGT1A1 gene, were treated with PEITC, TSB levels were reduced. Liver and intestinal UGT1A1 were induced, along with murine CYP2B10, a consensus CAR target gene. In both neonatal and adult hUGT1/Car−/− mice, PEITC was unable to induce CYP2B10. A similar result was observed following analysis of UGT1A1 expression in liver. However, TSB levels were still reduced in hUGT1/Car−/− neonatal mice because of ROS induction of intestinal UGT1A1. When oxidative stress was blocked by exposing mice to N-acetylcysteine, induction of liver UGT1A1 and CYP2B10 by PEITC was prevented. Thus, new findings in this report link an important role in CAR activation that is dependent upon oxidative stress.

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Section: Discussionmentioning

confidence: 71%

Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress

Yoda

Paszek

Konopnicki

et al. 2017

Sci Rep

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“…Under normal conditions, Nrf2 is retained cytoplasmically, bound to the cytoskeletal ubiquitin ligase Keap1. Upon stress exposure, Nrf2 releases, translocates to the nucleus, and forms a heterodimer with a small Muscle Aponeurosis Fibromatosis (Maf-S) protein [6] binding to AREs upstream of a battery of antioxidant genes ( Figure 1) including GSTs [7][8][9], carboxylesterases [10], cytochromes p450 [11] and ABC transporters [12] and is involved in regulation of the proteasome, serving to degrade damaged proteins and enzymes following stress-induced damage [13]. In Drosophila the insect Nrf2 ortholog Cap collar isofor C, (CncC), is known to have a central role in both development and the stress response [5,14].…”

Section: Cncc:maf Regulates Insecticide Resistance and Resistance-assmentioning

confidence: 99%

Regulating resistance: CncC:Maf, antioxidant response elements and the overexpression of detoxification genes in insecticide resistance

Wilding

2018

Current Opinion in Insect Science

102

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Although genetic and genomic tools have greatly furthered our understanding of resistance-associated mutations in molecular target sites of insecticides, the genomic basis of transcriptional regulation of detoxification loci in insect pests and vectors remains relatively unexplored. Recent work using RNAi, reporter assays and comparative genomics are beginning to reveal the molecular architecture of this response, identifying critical transcription factors and their binding sites. Central to this is the insect ortholog of the mammalian transcription factor Nrf2, Cap 'n' Collar isoform-C (CncC) which as a heterodimer with Maf-S regulates the transcription of phase I, II and III detoxification loci in a range of insects, with CncC knockdown or upregulation directly affecting phenotypic resistance. CncC:Maf binds to specific antioxidant response element sequences upstream of detoxification genes to initiate transcription. Recent work is now identifying these binding sites for resistance-associated loci and, coupled with genome sequence data and reporter assays, enabling identification of polymorphisms in the CncC:Maf binding site which regulate the insecticide resistance phenotype.

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“…The outcome of crosstalk is either stimulatory or inhibitory. The transcriptional factors that potentiate the activity of CAR include HNF4α, CCAATenhancer-binding protein α (C/EBPα), activating transcription factor 5 (ATF5), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and hypoxia-inducible factor 1 (Hif1) [64][65][66][67] . Much of the crosstalk occurs between specific genes.…”

Section: Modulators Of Car Activitymentioning

confidence: 99%

Deciphering the roles of the constitutive androstane receptor in energy metabolism

et al. 2014

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The constitutive androstane receptor (CAR) is initially defined as a xenobiotic nuclear receptor that protects the liver from injury. Detoxification of damaging chemicals is achieved by CAR-mediated induction of drug-metabolizing enzymes and transporters. More recent research has implicated CAR in energy metabolism, suggesting a therapeutic potential for CAR in metabolic diseases, such as type 2 diabetes and obesity. A better understanding of the mechanisms by which CAR regulates energy metabolism will allow us to take advantage of its effectiveness while avoiding its side effects. This review summarizes the current progress on the regulation of CAR nuclear translocation, upstream modulators of CAR activity, and the crosstalk between CAR and other transcriptional factors, with the aim of elucidating how CAR regulates glucose and lipid metabolism.

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Possible involvement of nuclear factor erythroid 2-related factor 2 in the gene expression of Cyp2b10 and Cyp2a5

Cited by 26 publications

References 22 publications

Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress

Isothiocyanates induce UGT1A1 in humanized UGT1 mice in a CAR dependent fashion that is highly dependent upon oxidative stress

Regulating resistance: CncC:Maf, antioxidant response elements and the overexpression of detoxification genes in insecticide resistance

Deciphering the roles of the constitutive androstane receptor in energy metabolism

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