Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein1 in mouse embryo fibroblasts

Hayashi, Asako; Suzuki, Hiroshi; Itoh, Ken; Yamamoto, Masayuki; Sugiyama, Yuichi

doi:10.1016/j.bbrc.2003.09.086

Cited by 245 publications

(187 citation statements)

References 21 publications

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“…In mouse embryonic fibroblasts, it has been previously shown that Mrp1 is Nrf2-dependent. 59 In this study, the basal expression of Mrp1 in the liver is very low, and the Nrf2 dependence could not be determined (data not shown). Previous experiments using the KEAP1-overexpressing HepG2 cell line showed increases in the cellular content of the anionic dye C-369, suggesting that when increased KEAP1 sequesters and prevents Nrf2 transactivation, a decreased cellular efflux function can be observed.…”

Section: Discussionmentioning

confidence: 64%

Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway

et al. 2007

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Multidrug resistance-associated proteins (Mrps) are adenosine triphosphate-dependent transporters that efflux chemicals out of cells. In the liver, Mrp2 transports bilirubinglucuronide, glutathione (GSH), and drug conjugates into bile, whereas Mrp3 and Mrp4 efflux these entities into blood. The purpose of this study was to determine whether oxidative conditions (that is, the disruption of hepatic GSH synthesis) or the administration of nuclear factor-E2-related factor-2 (Nrf2)

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Section: Discussionmentioning

confidence: 64%

Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway

et al. 2007

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“…Moreover, targeted inactivation of C. elegans MRP1 resulted in increased sensitivity to the heavy metal ions Cd and As [12]. It is shown that upon entering cells, heavy metals can induce the production of reactive oxygen species, therefore activate the nuclear factor Nrf2, which is the key transcriptional factor of antioxidant responsive element (ARE)-driven genes including MRP1 [37]. An ARE element has been found in the human ABCC1 promoter sequence [38].…”

Section: Discussionmentioning

confidence: 99%

Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish

Long

Cui

2010

Mol Biol Rep

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ABCC1/MRP1 belongs to the ATP-binding cassette superfamily and its elevated expression is closely associated with the multidrug resistance of various tumor cells. In normal tissues, ABCC1 confers resistance to a wide variety of xenobiotics and toxicants, demonstrating its important roles in tissue defense. Here, we report the cloning and functional characterization of abcc1 gene in zebrafish. This gene is localized on zebrafish chromosome 3 and contains a 4,557 bp open-reading frame. The deduced polypeptide is composed of 1,518 amino acids, which shares 70% identity with human ABCC1. Phylogenetic analysis revealed that ABCC1 proteins from thirteen vertebrate species are highly conserved during evolution. Transcriptional expression of zebrafish abcc1 gene in developing embryos was examined by whole-mount in situ hybridization and real-time PCR. Transcripts of zebrafish abcc1 gene were detectable in four-cell stage embryos, indicating that this gene is maternally expressed. ABCC1 mRNAs were ubiquitously distributed in embryos before 12 h post-fertilization (hpf) and mainly localized in eyes and brain from 24 to 72 hpf, and in gills from 96 to 120 hpf. In addition, zebrafish abcc1 gene was highly expressed in 1-hpf embryos and detected in all adult tissues examined, with highest expression in testis and lowest in heart and liver. Exposure of ZF4 cells and embryos to CdCl 2 Á2.5H 2 O, HgCl 2 , Pb(NO 3 ) 2 , or Na 3 AsO 4 Á12H 2 O significantly induced transcriptional expression of abcc1 gene. Furthermore, overexpression of abcc1 improved the survival rates of embryos exposed to Cd, Hg or As, while overexpression of a abcc1 mutant (ABCC1-G1420D) sensitized zebrafish embryos to toxic metals. These data indicate that zebrafish ABCC1 has crucial roles in heavy metals detoxification.

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“…EpRE/Nrf2 signaling has been found to be responsible for the induction of many phase II and antioxidant genes in response to ROS or electrophiles, including NADPH:quinine oxidoreductase-1 (NQO1) [80], HO-1 [81,82], glutamate cysteine ligase [35,[49][50][51], GSH Stransferase [83], and multidrug resistance protein [84]. Here we demonstrated that the induction of one major type of mRNA of GGT, a key enzyme involved in GSH homeostasis and GSH S-conjugates metabolism, is also mediated through EpRE/Nrf2 signaling in response to electrophile (HNE).…”

Section: Discussionmentioning

confidence: 99%

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

Zhang

Liu

Dickinson

et al. 2006

Free Radical Biology and Medicine

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Abstractγ-Glutamyl transpeptidase (GGT) plays key roles in glutathione homeostasis and metabolism of glutathione S-conjugates. Rat GGT is transcribed via five tandemly arranged promoters into seven transcripts. The transcription of mRNAV is controlled by promoter 5. Previously we found that GGT mRNAV-2 was responsible for the induction of GGT in rat alveolar epithelial cells by 4-hydroxynonenal (HNE). In the current study, the underlying mechanism was investigated. Reporter deletion and mutation analysis demonstrated that an electrophile-response element (EpRE) in the proximal region of GGT promoter 5 (GP5) was responsible for the basal-and HNE-induced promoter activity. Gel-shift assays showed an increased binding activity of GP5 EpRE after HNE exposure. The nuclear content of NF-E2-related factor 2 (Nrf2) was significantly increased by HNE. The recruitment of Nrf2 to GP5 EpRE after HNE treatment was demonstrated by supershift and chromatin immunoprecipitation assays. The tissue expression pattern of GGT mRNA V was previously unknown. Using polymerase chain reaction, we found that GGT mRNAV-2 was expressed in many tissues in rat. Taken together, GGT mRNAV-2 is widely expressed in rat tissues and its basal and HNE-induced expression is mediated through EpRE/Nrf2 signaling.

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Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein1 in mouse embryo fibroblasts

Cited by 245 publications

References 21 publications

Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway

Oxidative and electrophilic stress induces multidrug resistance-associated protein transporters via the nuclear factor-E2-related factor-2 transcriptional pathway

Molecular analysis and heavy metal detoxification of ABCC1/MRP1 in zebrafish

γ-Glutamyl transpeptidase is induced by 4-hydroxynonenal via EpRE/Nrf2 signaling in rat epithelial type II cells

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