Cited by 3,999Genomics, phytochemicals, and oxidative stressGlutathione Transferases and PolymorphismsPharmacogenetics and Drug Metabolism

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An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements

Itoh, Ken, Chiba, Tomoki, Takahashi, Satoru, Ishii, Tetsuro, Igarashi, Kazuhiko, Katoh, Yasutake, Oyake, Tatsuya, Hayashi, Norio, Satoh, Kimihiko, Hatayama, Ichiro, Yamamoto, Masayuki, Nabeshima, Yo-ichi·1997·Biochemical and Biophysical Research Communications

DOI 10.1006/bbrc.1997.6943

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Abstract

The induction of phase II detoxifying enzymes is an important defense mechanism against intake of xenobiotics. While this group of enzymes is believed to be under the transcriptional control of antioxidant response elements (AREs), this contention is experimentally unconfirmed. Since the ARE resembles the binding sequence of erythroid transcription factor NF-E2, we investigated the possibility that the phase II enzyme genes might be regulated by transcription factors that also bind to the NF-E2 sequence. The expression profiles of a number of transcription factors suggest that an Nrf2/small Maf heterodimer is the most likely candidate to fulfill this role in vivo. To directly test these questions, we disrupted the murine nrf2 gene in vivo. While the expression of phase II enzymes (e.g., glutathione S-transferase and NAD(P)H: quinone oxidoreductase) was markedly induced by a phenolic antioxidant in vivo in both wild type and heterozygous mutant mice, the induction was largely eliminated in the liver and intestine of homozygous nrf2-mutant mice. Nrf2 was found to bind to the ARE with high affinity only as a heterodimer with a small Maf protein, suggesting that Nrf2/small Maf activates gene expression directly through the ARE. These results demonstrate that Nrf2 is essential for the transcriptional induction of phase II enzymes and the presence of a coordinate transcriptional regulatory mechanism for phase II enzyme genes. The nrf2-deficient mice may prove to be a very useful model for the in vivo analysis of chemical carcinogenesis and resistance to anti-cancer drugs.

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Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,515
Glutathione Transferases—Structure and Catalytic Activit
Mannervik, B., Danielson, U. H., & KETTERER, B. (1988) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238809088226 · Cited by 1,759
Isolation of NF-E2-related factor 2 (Nrf2), a NF-E2-like basic leucine zipper transcriptional activator that binds to the tandem NF-E2/AP1 repeat of the beta-globin locus control region
Moi, P., Chan, K., Asunis, I., Cao, A., & Kan, Y. W. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.21.9926 · Cited by 1,607
The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity
Rushmore, T. H., Morton, M. R., & Pickett, C. B. (1991) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99004-6 · Cited by 1,464
HPRT-deficient (Lesch–Nyhan) mouse embryos derived from germline colonization by cultured cells
Hooper, M., Hardy, K., Handyside, A. H., Hunter, S., & Monk, M. (1987) · Nature · doi:10.1038/326292a0 · Cited by 1,218
The Role of Glutathione and Glutathione S-Transferases in the Metabolism of Chemical Carcinogens and Other Electrophilic Agents
Chasseaud, L. F. (1979) · Advances in cancer research · doi:10.1016/s0065-230x(08)60848-9 · Cited by 1,165
Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase 1 gene
Radjendirane, V., & Jaiswal, A. K. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14960 · Cited by 1,034
Toxicology and biochemistry of butylated hydroxyanisole and butylated hydroxytoluene
Branen, A. L. (1975) · Journal of the American Oil Chemists Society · doi:10.1007/bf02901825 · Cited by 768
Bach Proteins Belong to a Novel Family of BTB-Basic Leucine Zipper Transcription Factors That Interact with MafK and Regulate Transcription through the NF-E2 Site
Oyake, T., Itoh, K., Motohashi, H., Hayashi, N., Hoshino, H., Nishizawa, M., Yamamoto, M. P., & Igarashi, K. (1996) · Molecular and Cellular Biology · doi:10.1128/mcb.16.11.6083 · Cited by 656
NRF2, a member of the NFE2 family of transcription factors, is not essential for murine erythropoiesis, growth, and development
Chan, K., Lu, R., Chang, J. C., & Kan, Y. W. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.24.13943 · Cited by 643
Erythroid transcription factor NF-E2 is a haematopoietic-specific basic–leucine zipper protein
Andrews, N. C., Erdjument‐Bromage, H., Davidson, M. B., Tempst, P., & Orkin, S. H. (1993) · Nature · doi:10.1038/362722a0 · Cited by 637
Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants.
Rushmore, T. H., & Pickett, C. B. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)77351-1 · Cited by 522
Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis.
Satoh, K., Kitahara, A., Soma, Y., Inaba, Y., Hatayama, I., & Sato, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.3964 · Cited by 494
Regulation of transcription by dimerization of erythroid factor NF-E2 p45 with small Maf proteins
Igarashi, K., Kataokat, K., Itoh, K., Hayashi, N., Nishizawa, M., & Yamamoto, M. (1994) · Nature · doi:10.1038/367568a0 · Cited by 442
Cloning and Characterization of a Novel Erythroid Cell-Derived CNC Family Transcription Factor Heterodimerizing with the Small Maf Family Proteins
Itoh, K., Igarashi, K., Hayashi, N., Nishizawa, M., & Yamamoto, M. P. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.8.4184 · Cited by 438
Maf nuclear oncoprotein recognizes sequences related to an AP-1 site and forms heterodimers with both Fos and Jun
Kataoka, K., Noda, M., & Nishizawa, M. (1994) · Molecular and Cellular Biology · doi:10.1128/mcb.14.1.700 · Cited by 436
Chemical and molecular regulation of enzymes that detoxify carcinogens.
Prestera, T., Holtzclaw, W. D., Zhang, Y., & Talalay, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.7.2965 · Cited by 416
Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast.
Chan, J. Y., Han, X. L., & Kan, Y. W. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.23.11371 · Cited by 342
Inhibitors of Chemical Carcinogenesis
Wattenberg, L. W. (1978) · Advances in cancer research · doi:10.1016/s0065-230x(08)60088-3 · Cited by 303
Glutathione S-transferases: role in alkylating agent resistance and possible target for modulation chemotherapy--a review.
Waxman, D. J. (1990) · PubMed · Cited by 258
The ubiquitous subunit of erythroid transcription factor NF-E2 is a small basic-leucine zipper protein related to the v-maf oncogene.
Andrews, N. C., Kotkow, K. J., Ney, P. A., Erdjument‐Bromage, H., Tempst, P., & Orkin, S. H. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.24.11488 · Cited by 244
Two adjacent AP-1-like binding sites form the electrophile-responsive element of the murine glutathione S-transferase Ya subunit gene.
Friling, R. S., Bergelson, S., & Daniel, V. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.2.668 · Cited by 229
Small Maf Proteins Heterodimerize with Fos and May Act as Competitive Repressors of the NF-E2 Transcription Factor
Kataoka, K., Igarashi, K., Itoh, K., Fujiwara, K. T., Noda, M., Yamamoto, M. P., & Nishizawa, M. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.4.2180 · Cited by 217
Glutathione-S-transferase pi as a determinant of drug resistance in transfectant cell lines.
Nakagawa, K., Saijo, N., Tsuchida, S., Sakai, M., Tsunokawa, Y., Yokota, J., Muramatsu, M., Sato, K., Terada, M., & Tew, K. D. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39562-6 · Cited by 197
Induction of Phase I and Phase II Drug-Metabolizing Enzyme mRNA, Protein, and Activity by BHA, Ethoxyquin, and Oltipraz
Buetler, T. M., Gallagher, E. P., Wang, C. H., Stahl, D., Hayes, J. D., & Eaton, D. L. (1995) · Toxicology and Applied Pharmacology · doi:10.1006/taap.1995.1207 · Cited by 184
Structural and functional analysis of an enhancer GPEI having a phorbol 12-O-tetradecanoate 13-acetate responsive element-like sequence found in the rat glutathione transferase P gene
Okuda, A., Imagawa, M., Maeda, Y., Sakai, M., & Muramatsu, M. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84795-6 · Cited by 151
Expression of recombinant glutathione S-transferase pi, Ya, or Yb1 confers resistance to alkylating agents.
Puchalski, R. B., & Fahl, W. E. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.7.2443 · Cited by 147
ARE- and TRE-mediated Regulation of Gene Expression
Xie, T., Belinsky, M. G., Xu, Y., & Jaiswal, A. K. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.12.6894 · Cited by 142
Cloning and functional characterization of LCR-F1: a bZIP transcription factor that activates erythroid-specific, human globin gene expression
Caterina, J. J., Donze, D., Sun, C., Ciavatta, D. J., & Townes, T. M. (1994) · Nucleic Acids Research · doi:10.1093/nar/22.12.2383 · Cited by 138
The structure of the rat glutathione S-transferase P gene and related pseudogenes.
Okuda, A., Sakai, M., & Muramatsu, M. (1987) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)61435-8 · Cited by 131
Segmentally restricted, cephalic expression of a leucine zipper gene during Drosophila embryogenesis
Mohler, J., Vani, K., Leung, S., & Epstein, A. (1991) · Mechanisms of Development · doi:10.1016/0925-4773(91)90086-l · Cited by 129
酵母での遺伝的選択によるNF-E2関連転写因子、Nrf1のクローニング
Chan, J. Y., X‐L, H., & W, K. Y. (1993) · Cited by 123
Human small Maf proteins form heterodimers with CNC family transcription factors and recognize the NF-E2 motif
Toki, T., Itoh, J., Kitazawa, J., Arai, K., Hatakeyama, K., Akasaka, J.-I., Igarashi, K., Nomura, N., Yokoyama, M., Yamamoto, M. P., et al. (1997) · Oncogene · doi:10.1038/sj.onc.1201024 · Cited by 116
Antioxidant-Inducible Genes
Primiano, T., Sutter, T. R., & Kensler, T. W. (1996) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60989-8 · Cited by 112
Developmental and hormonal regulation of the major form of hepatic glutathione S-transferase in male mice
Hatayama, I., Satoh, K., & Sato, K. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)90771-0 · Cited by 108
Molecular Cloning of a Putative Novel Human bZIP Transcription Factor on Chromosome 17q22
Luna, L., Johnsen, Ø., Skartlien, A. H., Pédeutour, F., Turc‐Carel, C., Prydz, H., & Kolstø, A. (1994) · Genomics · doi:10.1006/geno.1994.1428 · Cited by 81
Tissue-specific induction of murine glutathione transferase mRNAs by butylated hydroxyanisole.
Pearson, W. R., Reinhart, J., Sisk, S. C., Anderson, K., & Adler, P. N. (1988) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)37708-1 · Cited by 76
cDNA cloning of murine Nrf 2 gene, coding for a p45 NF-E2 related transcription factor.
Chui, D. H. K., Tang, W.-Z., & Orkin, S. H. (1995) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1006/bbrc.1995.1467 · Cited by 65
Differential induction of class Alpha glutathione S-transferases in mouse liver by the anticarcinogenic antioxidant butylated hydroxyanisole. Purification and characterization of glutathione S-transferase Ya1Ya1
McLellan, L. I., & Hayes, J. D. (1989) · Biochemical Journal · doi:10.1042/bj2630393 · Cited by 63
Isolation, Characterization, and Expression in Escherichia coli of Two Murine Mu Class Glutathione S-Transferase cDNAs Homologous to the Rat Subunits 3 (Yb1) and 4 (Yb2)
Townsend, A. J., Goldsmith, M. E., Pickett, C. B., & Cowan, K. H. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(20)88223-4 · Cited by 57
Oxidative stress induces the levels of a MAFG homolog in hamster HA-1 cells
Crawford, D. R., Leahy, K. P., Wang, Y., Schools, G. P., Kochheiser, J. C., & Davies, K. J. A. (1996) · Free Radical Biology and Medicine · doi:10.1016/0891-5849(96)00160-8 · Cited by 57
Free radical intermediates during peroxidase oxidation of 2-t-butyl-4-methoxyphenol, 2,6-di-t-butyl-4-methylphenol, and related phenol compounds
Valoti, M., Sipe, H. J., Sgaragli, G., & Mason, R. P. (1989) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(89)90126-4 · Cited by 56
The peroxidase-dependent activation of butylated hydroxyanisole and butylated hydroxytoluene (BHT) to reactive intermediates
Thompson, D. C., N, Y., & Trush, M. A. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)84946-3 · Cited by 52
Two murine GSTpi genes are arranged in tandem and are differentially expressed.
Xu, X. P., & Stambrook, P. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43807-0 · Cited by 30
Expression of rat liver NAD(P)H:quinone-acceptor oxidoreductase in Escherichia coli and mutagenesis in vitro at Arg-177
Chen, H. H., X, J., Forrest, G. L., Deng, P. S.-K., Martino, P. A., Lee, T. D., & Chen, S. (1992) · Biochemical Journal · doi:10.1042/bj2840855 · Cited by 28
The Structure of Two Murine Class-Mu Glutathione Transferase Genes Coordinately Induced by Butylated Hydroxyanisole
Reinhart, J., & Pearson, W. R. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1299 · Cited by 24
Hepatic glutathione S-transferases in mice fed on a diet containing the anticarcinogenic antioxidant butylated hydroxyanisole. Isolation of mouse glutathione S-transferase heterodimers by gradient elution of the glutathione-Sepharose affinity matrix
Hayes, J. D., Kerr, L. A., Peacock, S. D., Cronshaw, A. D., & McLellan, L. I. (1991) · Biochemical Journal · doi:10.1042/bj2770501 · Cited by 24

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Kataoka, 1994, Mol. Cell. Biol., 14, 700
Chomczynski, 1987, Anal. Biochem., 162, 156, 10.1016/0003-2697(87)90021-2 · DOI
Waxam, 1990, Cancer Res., 50, 6449

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Authors: Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M., & Nabeshima, Y.-I.
Affiliations: University of Tsukuba (JP)
Japan Science and Technology Agency (JP)
Tohoku University (JP)
Hirosaki University (JP)
National Institute of Neuroscience (JP)
Corresponding author: Yamamoto, Masayuki
ORCID: Itoh, Ken
Chiba, Tomoki
Takahashi, Satoru
Igarashi, Kazuhiko
Hayashi, Norio
Satoh, Kimihiko
Yamamoto, Masayuki
Venue: Biochemical and Biophysical Research Communications
Publisher: Elsevier BV
Published: 1997-07
Volume: 236
Issue: 2
Pages: 313-322
ISSN: 0006-291X (ISSN-L)
DOI: 10.1006/bbrc.1997.6943
OpenAlex: W1991631628
Cited by: 3,999
References: 49
Citations by year: 2026: 138 · 2025: 154 · 2024: 165 · 2023: 187 · 2022: 196 · 2021: 222 · 2020: 257 · 2019: 224 · 2018: 197 · 2017: 236 · 2016: 227 · 2015: 194 · 2014: 169 · 2013: 206 · 2012: 160
FWCI: 8.67
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Biochemical and Biophysical Research Communications (publishedVersion)
PubMed (publishedVersion)
Funders: Japan Society for the Promotion of Science (RFTF96I00202)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Glutathione Transferases and Polymorphisms
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
Keywords: Nrf2, heterodimer, antioxidant response element, phase II enzymes, transcriptional regulation, Nrf2 knockout mice, glutathione S-transferase, NAD(P)H:quinone oxidoreductase, NF-E2, phenolic antioxidants, xenobiotic metabolism, chemical carcinogenesis, drug resistance
MeSH terms: Animals, Binding Sites, Butylated Hydroxyanisole, DNA-Binding Proteins, Glutathione Transferase, Heterozygote, Homozygote, Intestines, Liver, Male, Promoter Regions, Genetic, Quinone Reductases, Transcription Factors, Xenobiotics, Trans-Activators, Gene Expression Regulation, Enzymologic, Mice, Knockout, DNA Adducts, Dimerization, NF-E2-Related Factor 2, Mice

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An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements

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