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

Show all 49 references

Research works printed but not linked: 3

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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Suh, J. H., Shenvi, S. V., Dixon, B. M., Liu, H., Jaiswal, A. K., Liu, R.-M., & Hagen, T. M. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0400282101 · Cited by 774
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Ramsey, C. P., Glass, C. A., Montgomery, M. B., Lindl, K. A., Ritson, G. P., Chia, L. A., Hamilton, R. L., Chu, C. T., & Jordan-Sciutto, K. L. (2007) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/nen.0b013e31802d6da9 · Cited by 760
Particulate air pollutants and asthma
Li, N., Hao, M., Phalen, R. F., Hinds, W. C., & Nel, A. E. (2003) · Clinical Immunology · doi:10.1016/j.clim.2003.08.006 · Cited by 785
An important function of Nrf2 in combating oxidative stress: Detoxification of acetaminophen
Chan, K., Han, X.-D., & Kan, Y. W. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.081082098 · Cited by 766
Nrf2 as a Master Redox Switch in Turning on the Cellular Signaling Involved in the Induction of Cytoprotective Genes by Some Chemopreventive Phytochemicals
Surh, Y., Kundu, J. K., & Na, H. (2008) · Planta Medica · doi:10.1055/s-0028-1088302 · Cited by 758
Small Molecule Modulators of Keap1‐ Nrf2‐ ARE Pathway as Potential Preventive and Therapeutic Agents
Magesh, S., Chen, Y., & Hu, L. (2012) · Medicinal Research Reviews · doi:10.1002/med.21257 · Cited by 760
“Sesquiterpenes such as zumberone (18)180 and isoalantolactone (19),181 and terpenoids containing α,β-unsaturated fragrant aldehydes182 such as perillaldehyde (20) and citral (21) were shown to induce Nrf2-mediated expression of detoxifying enzymes.”
Background
PERK-dependent Activation of Nrf2 Contributes to Redox Homeostasis and Cell Survival following Endoplasmic Reticulum Stress
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An Important Role of Nrf2-ARE Pathway in the Cellular Defense Mechanism
Lee, J., & Johnson, J. A. (2004) · BMB Reports · doi:10.5483/bmbrep.2004.37.2.139 · Cited by 746
Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
Padmanabhan, B., Tong, K. I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.-I., Kobayashi, A., Yokoyama, S., & Yamamoto, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.013 · Cited by 735
The Roles of NRF2 in Modulating Cellular Iron Homeostasis
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High Sensitivity of Nrf2 Knockout Mice to Acetaminophen Hepatotoxicity Associated with Decreased Expression of ARE-Regulated Drug Metabolizing Enzymes and Antioxidant Genes
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An, J. H., & Blackwell, T. K. (2003) · Genes & Development · doi:10.1101/gad.1107803 · Cited by 741
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Calvert, J. W., Jha, S. K., Gundewar, S., Elrod, J. W., Ramachandran, A., Pattillo, C. B., Kevil, C. G., & Lefer, D. J. (2009) · Circulation Research · doi:10.1161/circresaha.109.199919 · Cited by 720
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Tu, W., Wang, H., Li, S., Liu, Q., & Sha, H. (2018) · Aging and Disease · doi:10.14336/ad.2018.0513 · Cited by 727
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Suzuki, T., Motohashi, H., & Yamamoto, M. (2013) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2013.04.005 · Cited by 680
Cellular response to endoplasmic reticulum stress: a matter of life or death
Boyce, M., & Yuan, J. (2006) · Cell Death and Differentiation · doi:10.1038/sj.cdd.4401817 · Cited by 681
Keap1/Nrf2 Signaling Regulates Oxidative Stress Tolerance and Lifespan in Drosophila
Sykiotis, G. P., & Bohmann, D. (2008) · Developmental Cell · doi:10.1016/j.devcel.2007.12.002 · Cited by 660
Multitargeting by curcumin as revealed by molecular interaction studies
Gupta, S. C., Prasad, S., Kim, J. H., Patchva, S., Webb, L. J., Priyadarsini, K. I., & Aggarwal, B. B. (2011) · Natural Product Reports · doi:10.1039/c1np00051a · Cited by 683
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Kwak, M.-K., Wakabayashi, N., Itoh, K., Motohashi, H., Yamamoto, M. P., & Kensler, T. W. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211898200 · Cited by 661
Role of NRF2 in Protection Against Hyperoxic Lung Injury in Mice
Cho, H., Jedlicka, A., Reddy, S. P., Kensler, T. W., Yamamoto, M. P., Zhang, L.-Y., & Kleeberger, S. R. (2002) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.26.2.4501 · Cited by 660
The Cap'n'Collar basic leucine zipper transcription factor Nrf2 (NF-E2 p45-related factor 2) controls both constitutive and inducible expression of intestinal detoxification and glutathione biosynthetic enzymes.
McMahon, M. J., Itoh, K., Yamamoto, M. P., Chanas, S. A., Henderson, C. J., McLellan, L. I., Wolf, C. R., Cavin, C., & Hayes, J. D. (2001) · PubMed · Cited by 657
Keap1 loss promotes Kras-driven lung cancer and results in dependence on glutaminolysis
Romero, R., Sayin, V. I., Davidson, S. M., Bauer, M. R., Singh, S. X., LeBoeuf, S. E., Karakousi, T. R., Ellis, D. C., Bhutkar, A., Sánchez-Rivera, F. J., et al. (2017) · Nature Medicine · doi:10.1038/nm.4407 · Cited by 652

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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