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Cited by 460Genomics, phytochemicals, and oxidative stressGlutathione Transferases and PolymorphismsPharmacogenetics and Drug Metabolism

Loss of the Nrf2 transcription factor causes a marked reduction in constitutive and inducible expression of the glutathione S-transferase Gsta1, Gsta2, Gstm1, Gstm2, Gstm3 and Gstm4 genes in the livers of male and female mice

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CHANAS, Simon A., JIANG, Qing, McMAHON, Michael, McWALTER, Gail K., McLELLAN, Lesley I., ELCOMBE, Clifford R., HENDERSON, Colin J., WOLF, C. Roland +4 more·2002·Biochemical Journal
DOI 10.1042/bj20020320PMC PMC1222698
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Abstract

Mice that lack the Nrf2 basic-region leucine-zipper transcription factor are more sensitive than wild-type (WT) animals to the cytotoxic and genotoxic effects of foreign chemicals and oxidants. To determine the basis for the decrease in tolerance of the Nrf2 homozygous null mice to xenobiotics, enzyme assay, Western blotting and gene-specific real-time PCR (TaqMan®) have been used to examine the extent to which hepatic expression of GSH-dependent enzymes is influenced by the transcription factor. The amounts of protein and mRNA for class Alpha, Mu and Pi glutathione S-transferases were compared between WT and Nrf2 knockout (KO) mice of both sexes under both constitutive and inducible conditions. Among the class Alpha and class Mu transferases, constitutive expression of Gsta1, Gsta2, Gstm1, Gstm2, Gstm3, Gstm4 and Gstm6 subunits was reduced in the livers of Nrf2 mutant mice to between 3% and 60% of that observed in WT mice. Induction of these subunits by butylated hydroxyanisole (BHA) was more marked in WT female mice than in WT male mice. TaqMan® analyses showed the increase in transferase mRNA caused by BHA was attenuated in Nrf2−/− mice, with the effect being most apparent in the case of Gsta1, Gstm1 and Gstm3. Amongst class Pi transferase subunits, the constitutive hepatic level of mRNA for Gstp1 and Gstp2 was not substantially affected in the KO mice, but their induction by BHA was dependent on Nrf2; this was more obvious in female mutant mice than in male mice. Nrf2 KO mice exhibited reduced constitutive expression of the glutamate cysteine ligase catalytic subunit, and, to a lesser extent, the expression of glutamate cysteine ligase modifier subunit. Little variation was observed in the levels of glutathione synthase in the different mouse lines. Thus the increased sensitivity of Nrf2−/− mice to xenobiotics can be partly attributed to a loss in constitutive expression of multiple GSH-dependent enzymes, which causes a reduction in intrinsic detoxification capacity in the KO animal. These data also indicate that attenuated induction of GSH-dependent enzymes in Nrf2−/− mice probably accounts for their failure to adapt to chronic exposure to chemical and oxidative stress.

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  • GSTMs are glutathione S-transferase family members within the mu subfamily that are activated upon WNT and NRF2 signaling.

    “GSTMs are glutathione S-transferase family members within the mu subfamily that are activated upon WNT and NRF2 signaling (40–43).”

    From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [40]

    The paper (pp. 405–416) identifies Gstm genes as Mu-class glutathione S-transferases and reports that their expression in mouse liver is reduced when Nrf2 is absent. It does not address activation by WNT signaling, so that part of the citing sentence is unsupported by this source. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • CTNNB1 transcriptionally activates NRF2, which in turn transcriptionally activates GSTMs.

    “Because CTNNB1 transcriptionally activates NRF2, which in turn transcriptionally activates GSTMs (40), antioxidant functions might be central to GSTM-induced carcinogenesis.”

    From The origin of hepatocellular carcinoma depends on metabolic zonation (2026) · cites this paper as [40]

    The paper’s opening summary reports that Nrf2 knockout reduces hepatic Gstm gene expression and attenuates induction of transferase mRNA, supporting the Nrf2-to-GSTM part of the claim. The passages do not address CTNNB1 or show that it transcriptionally activates NRF2; the paper’s results also establish an effect on GSTM expression rather than direct transcriptional activation. (LLM, conf=0.88)

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Cites

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Research works printed but not linked: 49

  1. Aoki Y., Sato H., Nishimura N., Takahashi S., Itoh K., Yamamoto M. Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol Appl Pharmacol. 2001 Jun 15;173(3):154–160. doi: 10.1006/taap.2001.9176. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  2. Bammler T. K., Smith C. A., Wolf C. R. Isolation and characterization of two mouse Pi-class glutathione S-transferase genes. Biochem J. 1994 Mar 1;298(Pt 2):385–390. doi: 10.1042/bj2980385. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  3. Buetler T. M., Slone D., Eaton D. L. Comparison of the aflatoxin B1-8,9-epoxide conjugating activities of two bacterially expressed alpha class glutathione S-transferase isozymes from mouse and rat. Biochem Biophys Res Commun. 1992 Oct 30;188(2):597–603. doi: 10.1016/0006-291x(92)91098-b. [DOI] [PubMed] [Google Scholar] · DOI
  4. Chan K., Han X. D., Kan Y. W. An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc Natl Acad Sci U S A. 2001 Apr 3;98(8):4611–4616. doi: 10.1073/pnas.081082098. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  5. Chan K., Kan Y. W. Nrf2 is essential for protection against acute pulmonary injury in mice. Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12731–12736. doi: 10.1073/pnas.96.22.12731. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  6. Cho Hye-Youn, Jedlicka Anne E., Reddy Sekhar P. M., Zhang Liu-Yi, Kensler Thomas W., Kleeberger Steven R. Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene. Am J Respir Cell Mol Biol. 2002 Jan;26(1):42–51. doi: 10.1165/ajrcmb.26.1.4536. [DOI] [PubMed] [Google Scholar] · DOI
  7. De Bruin W. C., Te Morsche R. H., Wagenmans M. J., Alferink J. C., Townsend A. J., Wieringa B., Peters W. H. Identification of a novel murine glutathione S-transferase class mu gene. Biochem J. 1998 Mar 1;330(Pt 2):623–626. doi: 10.1042/bj3300623. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  8. Dinkova-Kostova A. T., Massiah M. A., Bozak R. E., Hicks R. J., Talalay P. Potency of Michael reaction acceptors as inducers of enzymes that protect against carcinogenesis depends on their reactivity with sulfhydryl groups. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3404–3409. doi: 10.1073/pnas.051632198. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  9. Enomoto A., Itoh K., Nagayoshi E., Haruta J., Kimura T., O'Connor T., Harada T., Yamamoto M. High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of ARE-regulated drug metabolizing enzymes and antioxidant genes. Toxicol Sci. 2001 Jan;59(1):169–177. doi: 10.1093/toxsci/59.1.169. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
  10. Favreau L. V., Pickett C. B. The rat quinone reductase antioxidant response element. Identification of the nucleotide sequence required for basal and inducible activity and detection of antioxidant response element-binding proteins in hepatoma and non-hepatoma cell lines. J Biol Chem. 1995 Oct 13;270(41):24468–24474. doi: 10.1074/jbc.270.41.24468. [DOI] [PubMed] [Google Scholar] · DOI
  11. Favreau L. V., Pickett C. B. Transcriptional regulation of the rat NAD(P)H:quinone reductase gene. Identification of regulatory elements controlling basal level expression and inducible expression by planar aromatic compounds and phenolic antioxidants. J Biol Chem. 1991 Mar 5;266(7):4556–4561. [PubMed] [Google Scholar]
  12. Friling R. S., Bensimon A., Tichauer Y., Daniel V. Xenobiotic-inducible expression of murine glutathione S-transferase Ya subunit gene is controlled by an electrophile-responsive element. Proc Natl Acad Sci U S A. 1990 Aug;87(16):6258–6262. doi: 10.1073/pnas.87.16.6258. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  13. Fulcher K. D., Welch J. E., Klapper D. G., O'Brien D. A., Eddy E. M. Identification of a unique mu-class glutathione S-transferase in mouse spermatogenic cells. Mol Reprod Dev. 1995 Dec;42(4):415–424. doi: 10.1002/mrd.1080420407. [DOI] [PubMed] [Google Scholar] · DOI
  14. Hayes J. D., Chanas S. A., Henderson C. J., McMahon M., Sun C., Moffat G. J., Wolf C. R., Yamamoto M. The Nrf2 transcription factor contributes both to the basal expression of glutathione S-transferases in mouse liver and to their induction by the chemopreventive synthetic antioxidants, butylated hydroxyanisole and ethoxyquin. Biochem Soc Trans. 2000 Feb;28(2):33–41. doi: 10.1042/bst0280033. [DOI] [PubMed] [Google Scholar] · DOI
  15. Hayes J. D., Judah D. J., Neal G. E., Nguyen T. Molecular cloning and heterologous expression of a cDNA encoding a mouse glutathione S-transferase Yc subunit possessing high catalytic activity for aflatoxin B1-8,9-epoxide. Biochem J. 1992 Jul 1;285(Pt 1):173–180. doi: 10.1042/bj2850173. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  16. Hayes J. D., Kerr L. A., Peacock S. D., Cronshaw A. D., McLellan L. I. 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. Biochem J. 1991 Jul 15;277(Pt 2):501–512. doi: 10.1042/bj2770501. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  17. Hayes J. D., McLellan L. I. Glutathione and glutathione-dependent enzymes represent a co-ordinately regulated defence against oxidative stress. Free Radic Res. 1999 Oct;31(4):273–300. doi: 10.1080/10715769900300851. [DOI] [PubMed] [Google Scholar] · DOI
  18. Hayes J. D., McMahon M. Molecular basis for the contribution of the antioxidant responsive element to cancer chemoprevention. Cancer Lett. 2001 Dec 28;174(2):103–113. doi: 10.1016/s0304-3835(01)00695-4. [DOI] [PubMed] [Google Scholar] · DOI
  19. Hayes J. D., Pulford D. J. The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol. 1995;30(6):445–600. doi: 10.3109/10409239509083491. [DOI] [PubMed] [Google Scholar] · DOI
  20. He C. H., Gong P., Hu B., Stewart D., Choi M. E., Choi A. M., Alam J. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J Biol Chem. 2001 Mar 26;276(24):20858–20865. doi: 10.1074/jbc.M101198200. [DOI] [PubMed] [Google Scholar] · DOI
  21. Hu X., Benson P. J., Srivastava S. K., Mack L. M., Xia H., Gupta V., Zaren H. A., Singh S. V. Glutathione S-transferases of female A/J mouse liver and forestomach and their differential induction by anti-carcinogenic organosulfides from garlic. Arch Biochem Biophys. 1996 Dec 15;336(2):199–214. doi: 10.1006/abbi.1996.0550. [DOI] [PubMed] [Google Scholar] · DOI
  22. Hu X., Seidel A., Frank H., Srivastava S. K., Xia H., Pal A., Zheng S., Oesch F., Singh S. V. Differential enantioselectivity of murine glutathione S-transferase isoenzymes in the glutathione conjugation of trans-3,4-dihydroxy-1, 2-oxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene stereoisomers. Arch Biochem Biophys. 1998 Oct 1;358(1):40–48. doi: 10.1006/abbi.1998.0840. [DOI] [PubMed] [Google Scholar] · DOI
  23. Hu X., Srivastava S. K., Xia H., Awasthi Y. C., Singh S. V. An alpha class mouse glutathione S-transferase with exceptional catalytic efficiency in the conjugation of glutathione with 7beta, 8alpha-dihydroxy-9alpha,10alpha-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene. J Biol Chem. 1996 Dec 20;271(51):32684–32688. doi: 10.1074/jbc.271.51.32684. [DOI] [PubMed] [Google Scholar] · DOI
  24. Ishii T., Itoh K., Takahashi S., Sato H., Yanagawa T., Katoh Y., Bannai S., Yamamoto M. Transcription factor Nrf2 coordinately regulates a group of oxidative stress-inducible genes in macrophages. J Biol Chem. 2000 May 26;275(21):16023–16029. doi: 10.1074/jbc.275.21.16023. [DOI] [PubMed] [Google Scholar] · DOI
  25. Johnson J. A., Finn K. A., Siegel F. L. Tissue distribution of enzymic methylation of glutathione S-transferase and its effects on catalytic activity. Methylation of glutathione S-transferase 11-11 inhibits conjugating activity towards 1-chloro-2,4-dinitrobenzene. Biochem J. 1992 Feb 15;282(Pt 1):279–289. doi: 10.1042/bj2820279. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  26. Kwak M. K., Egner P. A., Dolan P. M., Ramos-Gomez M., Groopman J. D., Itoh K., Yamamoto M., Kensler T. W. Role of phase 2 enzyme induction in chemoprotection by dithiolethiones. Mutat Res. 2001 Sep 1;480-481:305–315. doi: 10.1016/s0027-5107(01)00190-7. [DOI] [PubMed] [Google Scholar] · DOI
  27. McLellan L. I., Harrison D. J., Hayes J. D. Modulation of glutathione S-transferases and glutathione peroxidase by the anticarcinogen butylated hydroxyanisole in murine extrahepatic organs. Carcinogenesis. 1992 Dec;13(12):2255–2261. doi: 10.1093/carcin/13.12.2255. [DOI] [PubMed] [Google Scholar] · DOI
  28. McLellan L. I., Hayes J. D. 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. Biochem J. 1989 Oct 15;263(2):393–402. doi: 10.1042/bj2630393. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  29. McLellan L. I., Hayes J. D. Sex-specific constitutive expression of the pre-neoplastic marker glutathione S-transferase, YfYf, in mouse liver. Biochem J. 1987 Jul 15;245(2):399–406. doi: 10.1042/bj2450399. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  30. McLellan L. I., Kerr L. A., Cronshaw A. D., Hayes J. D. Regulation of mouse glutathione S-transferases by chemoprotectors. Molecular evidence for the existence of three distinct alpha-class glutathione S-transferase subunits, Ya1, Ya2, and Ya3, in mouse liver. Biochem J. 1991 Jun 1;276(Pt 2):461–469. doi: 10.1042/bj2760461. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  31. McMahon M., Itoh K., Yamamoto M., Chanas S. A., Henderson C. J., McLellan L. I., Wolf C. R., Cavin C., Hayes J. D. 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. Cancer Res. 2001 Apr 15;61(8):3299–3307. [PubMed] [Google Scholar]
  32. Mitchell A. E., Morin D., Lakritz J., Jones A. D. Quantitative profiling of tissue- and gender-related expression of glutathione S-transferase isoenzymes in the mouse. Biochem J. 1997 Jul 1;325(Pt 1):207–216. doi: 10.1042/bj3250207. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  33. Morimitsu Yasujiro, Nakagawa Yoko, Hayashi Kazuhiro, Fujii Hiroyuki, Kumagai Takeshi, Nakamura Yoshimasa, Osawa Toshihiko, Horio Fumihiko, Itoh Ken, Iida Katsuyuki. A sulforaphane analogue that potently activates the Nrf2-dependent detoxification pathway. J Biol Chem. 2001 Nov 12;277(5):3456–3463. doi: 10.1074/jbc.M110244200. [DOI] [PubMed] [Google Scholar] · DOI
  34. Nguyen T., Huang H. C., Pickett C. B. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J Biol Chem. 2000 May 19;275(20):15466–15473. doi: 10.1074/jbc.M000361200. [DOI] [PubMed] [Google Scholar] · DOI
  35. Pearson W. R., Reinhart J., Sisk S. C., Anderson K. S., Adler P. N. Tissue-specific induction of murine glutathione transferase mRNAs by butylated hydroxyanisole. J Biol Chem. 1988 Sep 15;263(26):13324–13332. [PubMed] [Google Scholar]
  36. Peters M. M., Lau S. S., Dulik D., Murphy D., van Ommen B., van Bladeren P. J., Monks T. J. Metabolism of tert-butylhydroquinone to S-substituted conjugates in the male Fischer 344 rat. Chem Res Toxicol. 1996 Jan-Feb;9(1):133–139. doi: 10.1021/tx950122i. [DOI] [PubMed] [Google Scholar] · DOI
  37. Prestera T., Holtzclaw W. D., Zhang Y., Talalay P. Chemical and molecular regulation of enzymes that detoxify carcinogens. Proc Natl Acad Sci U S A. 1993 Apr 1;90(7):2965–2969. doi: 10.1073/pnas.90.7.2965. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  38. Ramos-Gomez M., Kwak M. K., Dolan P. M., Itoh K., Yamamoto M., Talalay P., Kensler T. W. Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factor-deficient mice. Proc Natl Acad Sci U S A. 2001 Mar 13;98(6):3410–3415. doi: 10.1073/pnas.051618798. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
  39. Reinhart J., Pearson W. R. The structure of two murine class-mu glutathione transferase genes coordinately induced by butylated hydroxyanisole. Arch Biochem Biophys. 1993 Jun;303(2):383–393. doi: 10.1006/abbi.1993.1299. [DOI] [PubMed] [Google Scholar] · DOI
  40. Rowe J. D., Patskovsky Y. V., Patskovska L. N., Novikova E., Listowsky I. Rationale for reclassification of a distinctive subdivision of mammalian class Mu glutathione S-transferases that are primarily expressed in testis. J Biol Chem. 1998 Apr 17;273(16):9593–9601. doi: 10.1074/jbc.273.16.9593. [DOI] [PubMed] [Google Scholar] · DOI
  41. Rushmore T. H., Morton M. R., Pickett C. B. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem. 1991 Jun 25;266(18):11632–11639. [PubMed] [Google Scholar]
  42. Sisk S. C., Pearson W. R. Differences in induction by xenobiotics in murine tissues and the Hepa1c1c7 cell line of mRNAs encoding glutathione transferase, quinone reductase, and CYP1A P450s. Pharmacogenetics. 1993 Aug;3(4):167–181. doi: 10.1097/00008571-199308000-00001. [DOI] [PubMed] [Google Scholar] · DOI
  43. Townsend A. J., Fields W. R., Haynes R. L., Doss A. J., Li Y., Doehmer J., Morrow C. S. Chemoprotective functions of glutathione S-transferases in cell lines induced to express specific isozymes by stable transfection. Chem Biol Interact. 1998 Apr 24;111-112:389–407. doi: 10.1016/s0009-2797(97)00175-0. [DOI] [PubMed] [Google Scholar] · DOI
  44. Townsend A. J., Goldsmith M. E., Pickett C. B., Cowan K. H. 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). J Biol Chem. 1989 Dec 25;264(36):21582–21590. [PubMed] [Google Scholar]
  45. Venugopal R., Jaiswal A. K. Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreductase1 gene. Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14960–14965. doi: 10.1073/pnas.93.25.14960. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  46. Wild A. C., Mulcahy R. T. Regulation of gamma-glutamylcysteine synthetase subunit gene expression: insights into transcriptional control of antioxidant defenses. Free Radic Res. 2000 Apr;32(4):281–301. doi: 10.1080/10715760000300291. [DOI] [PubMed] [Google Scholar] · DOI
  47. Xu X., Stambrook P. J. Two murine GSTpi genes are arranged in tandem and are differentially expressed. J Biol Chem. 1994 Dec 2;269(48):30268–30273. [PubMed] [Google Scholar]
  48. Yoshioka K., Deng T., Cavigelli M., Karin M. Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. Proc Natl Acad Sci U S A. 1995 May 23;92(11):4972–4976. doi: 10.1073/pnas.92.11.4972. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
  49. Zhu M., Fahl W. E. Functional characterization of transcription regulators that interact with the electrophile response element. Biochem Biophys Res Commun. 2001 Nov 23;289(1):212–219. doi: 10.1006/bbrc.2001.5944. [DOI] [PubMed] [Google Scholar] · DOI

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Authors
CHANAS, S. A., JIANG, Q., McMAHON, M., McWALTER, G. K., McLELLAN, L. I., ELCOMBE, C. R., HENDERSON, C. J., WOLF, C. R., MOFFAT, G. J., ITOH, K., YAMAMOTO, M., & HAYES, J. D.
Affiliations
  • University of Dundee (GB)
  • Biomedical Research Centre, Ninewells Hospital and Medical School, University of Dundee, Dundee DD1 9SY, Scotland, U.K.
  • Cancer Research UK (GB)
  • Syngenta (United Kingdom) (GB)
  • University of Tsukuba (JP)
ORCID
Venue
Biochemical Journal
Publisher
Portland Press Ltd.
Published
2002-07-15
Volume
365
Issue
2
Pages
405-416
ISSN
  • 0264-6021 (ISSN-L)
  • 1470-8728
DOI
10.1042/bj20020320
PMC
PMC1222698
OpenAlex
W2048700223
Cited by
460
References
1
Citations by year
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FWCI
7.07
Type
journal article
Language
en
Open access
Locations
  • Biochemical Journal (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion)
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
glutathione S-transferase, GSTA1, GSTA2, GSTM1, GSTM2, GSTM3, GSTM4, GSTP1, glutathione S-transferase induction, butylated hydroxyanisole, gamma-glutamylcysteine synthetase, glutathione synthetase, hepatic detoxification, sex differences, liver
MeSH terms
Amino Acid Sequence, Animals, Base Sequence, Cloning, Molecular, DNA-Binding Proteins, Female, Glutathione Transferase, Liver, Male, Molecular Sequence Data, RNA, Messenger, Blotting, Western, DNA Probes, Trans-Activators, Sequence Homology, Amino Acid, DNA Primers, Mice, Knockout, NF-E2-Related Factor 2, Mice

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