BMB Reports

생화학분자생물학회 (Korean Society for Biochemistry and Molecular Biology)
권호 표지
DOI QR코드

DOI QR Code

An Important Role of Nrf2-ARE Pathway in the Cellular Defense Mechanism

  • Lee, Jong-Min (School of Pharmacy, University of Wisconsin) ;
  • Johnson, Jeffrey A. (School of Pharmacy, University of Wisconsin)
  • 발행 : 2004.03.31
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

The antioxidant responsive element (ARE) is a cis-acting regulatory element of genes encoding phase II detoxification enzymes and antioxidant proteins, such as NAD(P)H: quinone oxidoreductase 1, glutathione S-transferases, and glutamate-cysteine ligase. Interestingly, it has been reported that Nrf2 (NF-E2-related factor 2) regulates a wide array of ARE-driven genes in various cell types. Nrf2 is a basic leucine zipper transcription factor, which was originally identified as a binding protein of locus control region of ss-globin gene. The DNA binding sequence of Nrf2 and ARE sequence are very similar, and many studies demonstrated that Nrf2 binds to the ARE sites leading to up-regulation of downstream genes. The function of Nrf2 and its downstream target genes suggests that the Nrf2-ARE pathway is important in the cellular antioxidant defense system. In support of this, many studies showed a critical role of Nrf2 in cellular protection and anti-carcinogenicity, implying that the Nrf2-ARE pathway may serve as a therapeutic target for neurodegenerative diseases and cancers, in which oxidative stress is closely implicated.

키워드

참고문헌

  1. Aoki, Y., Sato, H., Nishimura, N., Takahashi, S., Itoh, K. and Yamamoto, M. (2001) Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol. Appl. Pharmacol. 173, 154-160. https://doi.org/10.1006/taap.2001.9176
  2. Chan, J. Y., Han, X. L. and Kan, Y. W. (1993) Cloning of Nrf1, an NF-E2-related transcription factor, by genetic selection in yeast. Proc. Natl. Acad. Sci. USA 90, 11371-11375. https://doi.org/10.1073/pnas.90.23.11371
  3. Chan, K., Han, X. D. and Kan, Y. W. (2001) An important function of Nrf2 in combating oxidative stress: detoxification of acetaminophen. Proc. Natl. Acad. Sci. USA 98, 4611-4616. https://doi.org/10.1073/pnas.081082098
  4. Chan, K. and Kan, Y. W. (1999) Nrf2 is essential for protection against acute pulmonary injury in mice. Proc. Natl. Acad. Sci. USA 96, 12731-12736. https://doi.org/10.1073/pnas.96.22.12731
  5. Cho, H. Y., Jedlicka, A. E., Reddy, S. P., Kensler, T. W., Yamamoto, M., Zhang, L. Y. and Kleeberger, S. R. (2002) Role of NRF2 in protection against hyperoxic lung injury in mice. Ame. J. Respir. Cell Mol. Biol. 26, 175-182. https://doi.org/10.1165/ajrcmb.26.2.4501
  6. Cullinan, S. B., Zhang, D., Hannink, M., Arvisais, E., Kaufman, R. J. and Diehl, J. A. (2003) Nrf2 is a direct PERK substrate and effector of PERK-dependent cell survival. Mol. Cell Biol. 23, 7198-7209. https://doi.org/10.1128/MCB.23.20.7198-7209.2003
  7. Duffy, S., So, A. and Murphy, T. H. (1998) Activation of endogenous antioxidant defenses in neuronal cells prevents free radical-mediated damage. J. Neurochem. 71, 69-77.
  8. Enomoto, A., Itoh, K., Nagayoshi, E., Haruta, J., Kimura, T., O'Connor, T., Harada, T. and Yamamoto, M. (2001) High sensitivity of Nrf2 knockout mice to acetaminophen hepatotoxicity associated with decreased expression of AREregulated drug metabolizing enzymes and antioxidant genes. Toxicol. Sci. 59, 169-177. https://doi.org/10.1093/toxsci/59.1.169
  9. Fahey, J. W., Haristoy, X., Dolan, P. M., Kensler, T. W., Scholtus, I., Stephenson, K. K., Talalay, P. and Lozniewski, A. (2002) Sulforaphane inhibits extracellular, intracellular, and antibioticresistant strains of Helicobacter pylori and prevents benzo(a)pyrene-induced stomach tumors. Proc. Natl. Acad. Sci. USA 99, 7610-7615. https://doi.org/10.1073/pnas.112203099
  10. Friling, R. S., Bensimon, A., Tichauer, Y. and Daniel, V. (1990) Xenobiotic-inducible expression of murine glutathione Stransferase Ya subunit gene is controlled by an electrophileresponsive element. Proc. Natl. Acad. Sci. USA 87, 6258-6262. https://doi.org/10.1073/pnas.87.16.6258
  11. Friling, R. S., Bergelson, S. and Daniel, V. (1992) Two adjacent AP-1-like binding sites form the electrophile-responsive element of the murine glutathione S-transferase Ya subunit gene. Proc. Natl. Acad. Sci. USA 89, 668-672. https://doi.org/10.1073/pnas.89.2.668
  12. Ishii, T., Itoh, K. and Yamamoto, M. (2002) Roles of Nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements. Methods Enzymol. 348, 182-190. https://doi.org/10.1016/S0076-6879(02)48637-5
  13. Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., Yamamoto, M. and Nabeshima, Y. (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236, 313-322. https://doi.org/10.1006/bbrc.1997.6943
  14. Kotlo, K. U., Yehiely, F., Efimova, E., Harasty, H., Hesabi, B., Shchors, K., Einat, P., Rozen, A., Berent, E. and Deiss, L. P. (2003) Nrf2 is an inhibitor of the Fas pathway as identified by Achilles' Heel Method, a new function-based approach to gene identification in human cells. Oncogene 22, 797-806. https://doi.org/10.1038/sj.onc.1206077
  15. Lee, J. M., Calkins, M. J., Chan, K., Kan, Y. W. and Johnson, J. A. (2003a) Identification of the NF-E2-related Factor-2-dependent Genes Conferring Protection against Oxidative Stress in Primary Cortical Astrocytes Using Oligonucleotide Microarray Analysis. J. Biol. Chem. 278, 12029-12038. https://doi.org/10.1074/jbc.M211558200
  16. Lee, J. M., Shih, A. Y., Murphy, T. H. and Johnson, J. A. (2003b) NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J. Biol. Chem. 278, 37948-37956. https://doi.org/10.1074/jbc.M305204200
  17. Li, J., Lee, J. M. and Johnson, J. A. (2002) Microarray analysis reveals an antioxidant responsive element-driven gene set involved in conferring protection from an oxidative stressinduced apoptosis in IMR-32 cells. J. Biol. Chem. 277, 388-394. https://doi.org/10.1074/jbc.M109380200
  18. Li, Y. and Jaiswal, A. K. (1992) Regulation of human NAD(P)H:quinone oxidoreductase gene. Role of AP1 binding site contained within human antioxidant response element. J. Biol. Chem. 267, 15097-15104.
  19. Moi, P., Chan, K., Asunis, I., Cao, A. and Kan, Y. W. (1994) 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. Proc. Natl. Acad. Sci. USA 91, 9926-9930. https://doi.org/10.1073/pnas.91.21.9926
  20. Morito, N., Yoh, K., Itoh, K., Hirayama, A., Koyama, A., Yamamoto, M. and Takahashi, S. (2003) Nrf2 regulates the sensitivity of death receptor signals by affecting intracellular glutathione levels. Oncogene 22, 9275-9281. https://doi.org/10.1038/sj.onc.1207024
  21. Murphy, T. H., De Long, M. J. and Coyle, J. T. (1991) Enhanced NAD(P)H:quinone reductase activity prevents glutamate toxicity produced by oxidative stress. J. Neurochem. 56, 990-995. https://doi.org/10.1111/j.1471-4159.1991.tb02019.x
  22. Nguyen, T. and Pickett, C. B. (1992) Regulation of rat glutathione S-transferase Ya subunit gene expression. DNA-protein interaction at the antioxidant responsive element. J. Biol. Chem. 267, 13535-13539.
  23. Nguyen, T., Rushmore, T. H. and Pickett, C. B. (1994) Transcriptional regulation of a rat liver glutathione S-transferase Ya subunit gene. Analysis of the antioxidant response element and its activation by the phorbol ester 12-Otetradecanoylphorbol- 13-acetate. J. Biol. Chem. 269, 13656-13662.
  24. Ohtsubo, T., Kamada, S., Mikami, T., Murakami, H. and Tsujimoto, Y. (1999) Identification of NRF2, a member of the NF-E2 family of transcription factors, as a substrate for caspase-3(-like) proteases. Cell Death Differ. 6, 865-872. https://doi.org/10.1038/sj.cdd.4400566
  25. Okuda, A., Imagawa, M., Maeda, Y., Sakai, M. and Muramatsu, M. (1989) 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. J. Biol. Chem. 264, 16919-16926.
  26. Ramos-Gomez, M., Kwak, M. K., Dolan, P. M., Itoh, K., Yamamoto, M., Talalay, P. and Kensler, T. W. (2001) Sensitivity to carcinogenesis is increased and chemoprotective efficacy of enzyme inducers is lost in nrf2 transcription factordeficient mice. Proc. Natl. Acad. Sci. USA 98, 3410-3415. https://doi.org/10.1073/pnas.051618798
  27. Rushmore, T. H. (1990) Transcriptional regulation of the rat glutathione S-transferase Ya subunit gene. Characterization of a xenobiotic-responsive element controlling inducible expression by phenolic antioxidants. J. Biol. Chem. 265, 14648-14653.
  28. Rushmore, T. H., Morton, M. R. and Pickett, C. B. (1991) The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J. Biol. Chem. 266, 11632-11639.
  29. Shih, A. Y., Johnson, D. A., Wong, G., Kraft, A. D., Jiang, L., Erb, H., Johnson, J. A. and Murphy, T. H. (2003) Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J. Neurosci. 23, 3394-3406.
  30. Venugopal, R. and Jaiswal, A. K. (1996) 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. USA 93, 14960-14965. https://doi.org/10.1073/pnas.93.25.14960
  31. Wang, B. and Williamson, G. (1994) Detection of a nuclear protein which binds specifically to the antioxidant responsive element (ARE) of the human NAD(P)H:quinone oxidoreductase gene. Biochim. Biophys. Acta 1219, 645-652. https://doi.org/10.1016/0167-4781(94)90223-2

피인용 문헌

  1. Activation of the Nuclear Factor E2-Related Factor 2/Antioxidant Response Element Pathway Is Neuroprotective after Spinal Cord Injury vol.29, pp.5, 2012, https://doi.org/10.1089/neu.2011.1922
  2. Binding Mode and Structure-Activity Relationships around Direct Inhibitors of the Nrf2-Keap1 Complex vol.9, pp.4, 2014, https://doi.org/10.1002/cmdc.201300525
  3. Activation of Nuclear Factor Erythroid 2-Related Factor 2 Cytoprotective Signaling by Curcumin Protect Primary Spinal Cord Astrocytes against Oxidative Toxicity vol.34, pp.8, 2011, https://doi.org/10.1248/bpb.34.1194
  4. Pyrroloquinoline Quinine Protects Rat Brain Cortex Against Acute Glutamate-Induced Neurotoxicity vol.38, pp.8, 2013, https://doi.org/10.1007/s11064-013-1068-2
  5. Hesperetin Suppresses Inflammatory Responses in Lipopolysaccharide-Induced RAW 264.7 Cells via the Inhibition of NF-κB and Activation of Nrf2/HO-1 Pathways 2016, https://doi.org/10.1007/s10753-016-0311-9
  6. Low fucose containing bacterial polysaccharide facilitate mitochondria-dependent ROS-induced apoptosis of human lung epithelial carcinoma via controlled regulation of MAPKs-mediated Nrf2/Keap1 homeostasis signaling vol.54, pp.12, 2015, https://doi.org/10.1002/mc.22236
  7. Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1 defence response pathway in CD-1 mice vol.243, pp.3, 2008, https://doi.org/10.1016/j.tox.2007.10.011
  8. Mechanism of Action of Nigella sativa on Human Colon Cancer Cells: the Suppression of AP-1 and NF-κB Transcription Factors and the Induction of Cytoprotective Genes vol.16, pp.17, 2015, https://doi.org/10.7314/APJCP.2015.16.17.7943
  9. Induction of heme oxygenase-1 in normal and malignant B lymphocytes by 15-deoxy-Δ12,14-prostaglandin J2 requires Nrf2 vol.262, pp.1, 2010, https://doi.org/10.1016/j.cellimm.2009.12.003
  10. Redox regulation of mitophagy in the lung during murine Staphylococcus aureus sepsis vol.78, 2015, https://doi.org/10.1016/j.freeradbiomed.2014.10.582
  11. Tissue and species distribution of the glutathione pathway transcriptome vol.36, pp.10-11, 2006, https://doi.org/10.1080/00498250600861793
  12. Diallyl sulfide enhances antioxidants and inhibits inflammation through the activation of Nrf2 against gentamicin-induced nephrotoxicity in Wistar rats vol.606, pp.1-3, 2009, https://doi.org/10.1016/j.ejphar.2008.12.055
  13. The FA pathway counteracts oxidative stress through selective protection of antioxidant defense gene promoters vol.119, pp.18, 2012, https://doi.org/10.1182/blood-2011-09-381970
  14. Scavenging of peroxynitrite-derived radicals by flavonoids may support endothelial NO synthase activity, contributing to the vascular protection associated with high fruit and vegetable intakes vol.70, pp.1, 2008, https://doi.org/10.1016/j.mehy.2005.09.058
  15. Nox4: A Hydrogen Peroxide-Generating Oxygen Sensor vol.53, pp.31, 2014, https://doi.org/10.1021/bi500331y
  16. Alteration of serum lipid profile, SRB1 loss, and impaired Nrf2 activation in CDKL5 disorder vol.86, 2015, https://doi.org/10.1016/j.freeradbiomed.2015.05.010
  17. Nrf-2 overexpression in mesenchymal stem cells reduces oxidative stress-induced apoptosis and cytotoxicity vol.17, pp.5, 2012, https://doi.org/10.1007/s12192-012-0331-9
  18. Boolean modeling and fault diagnosis in oxidative stress response vol.13, pp.Suppl 6, 2012, https://doi.org/10.1186/1471-2164-13-S6-S4
  19. Desoxyrhapontigenin up-regulates Nrf2-mediated heme oxygenase-1 expression in macrophages and inflammatory lung injury vol.2, 2014, https://doi.org/10.1016/j.redox.2014.02.001
  20. Oxidative Toxicity in Neurodegenerative Diseases: Role of Mitochondrial Dysfunction and Therapeutic Strategies vol.2011, 2011, https://doi.org/10.1155/2011/683728
  21. NRF2 Regulates HER2 and HER3 Signaling Pathway to Modulate Sensitivity to Targeted Immunotherapies vol.2016, 2016, https://doi.org/10.1155/2016/4148791
  22. Mitochondria and metazoan epigenesis vol.20, pp.3, 2009, https://doi.org/10.1016/j.semcdb.2009.02.002
  23. Chemical and Biological Assessment ofZiziphus jujubaFruits from China: Different Geographical Sources and Developmental Stages vol.61, pp.30, 2013, https://doi.org/10.1021/jf402379u
  24. Supplementation of a grape seed and grape marc meal extract decreases activities of the oxidative stress-responsive transcription factors NF-κB and Nrf2 in the duodenal mucosa of pigs vol.55, pp.1, 2013, https://doi.org/10.1186/1751-0147-55-18
  25. Velafermin (rhFGF-20) reduces the severity and duration of hamster cheek pouch mucositis induced by fractionated radiation vol.84, pp.5, 2008, https://doi.org/10.1080/09553000802007601
  26. Sulforaphane ameliorates the development of experimental autoimmune encephalomyelitis by antagonizing oxidative stress and Th17-related inflammation in mice vol.250, 2013, https://doi.org/10.1016/j.expneurol.2013.10.002
  27. Dapsone induces oxidative stress and impairs antioxidant defenses in rat liver vol.83, pp.5-6, 2008, https://doi.org/10.1016/j.lfs.2008.05.016
  28. MAP3K7 and GSTZ1 are associated with human longevity: a two-stage case–control study using a multilocus genotyping vol.35, pp.4, 2013, https://doi.org/10.1007/s11357-012-9416-8
  29. Naringin modulates oxidative stress and inflammation in 3-nitropropionic acid-induced neurodegeneration through the activation of nuclear factor-erythroid 2-related factor-2 signalling pathway vol.227, 2012, https://doi.org/10.1016/j.neuroscience.2012.07.060
  30. Discovery of direct inhibitors of Keap1–Nrf2 protein–protein interaction as potential therapeutic and preventive agents vol.5, pp.4, 2015, https://doi.org/10.1016/j.apsb.2015.05.008
  31. Involvement of Nrf2 signaling pathway in the neuroprotective activity of natural kaurane diterpenes vol.231, 2013, https://doi.org/10.1016/j.neuroscience.2012.10.018
  32. Protective effect of tert-butylhydroquinone on cerebral inflammatory response following traumatic brain injury in mice vol.42, pp.7, 2011, https://doi.org/10.1016/j.injury.2011.03.009
  33. Activation of Nrf2-ARE signal pathway protects the brain from damage induced by epileptic seizure vol.1544, 2014, https://doi.org/10.1016/j.brainres.2013.12.004
  34. Nrf2 is essential for the anti-inflammatory effect of carbon monoxide in LPS-induced inflammation vol.64, pp.7, 2015, https://doi.org/10.1007/s00011-015-0834-9
  35. Ellagic acid attenuates high-carbohydrate, high-fat diet-induced metabolic syndrome in rats vol.52, pp.2, 2013, https://doi.org/10.1007/s00394-012-0358-9
  36. A comparative study on the effect of algal and fish oil on viability and cell proliferation of Caco-2 cells vol.45, pp.5, 2007, https://doi.org/10.1016/j.fct.2006.10.017
  37. Endogenous Hydrogen Peroxide Regulates Glutathione Redox via Nuclear Factor Erythroid 2-Related Factor 2 Downstream of Phosphatidylinositol 3-Kinase during Muscle Differentiation vol.172, pp.6, 2008, https://doi.org/10.2353/ajpath.2008.070429
  38. Nrf2-induced antioxidant protection: A promising target to counteract ROS-mediated damage in neurodegenerative disease? vol.45, pp.10, 2008, https://doi.org/10.1016/j.freeradbiomed.2008.09.001
  39. Silencing of Hsp90 Chaperone Expression Protects Against 6-Hydroxydopamine Toxicity in PC12 Cells vol.52, pp.3, 2014, https://doi.org/10.1007/s12031-013-0163-9
  40. Eriodictyol attenuates cisplatin-induced kidney injury by inhibiting oxidative stress and inflammation vol.772, 2016, https://doi.org/10.1016/j.ejphar.2015.12.042
  41. Gene expression profiling and pathway network analysis of hepatic metabolic enzymes targeted by baicalein vol.140, pp.1, 2012, https://doi.org/10.1016/j.jep.2011.12.046
  42. Antioxidative stress effect of phosphoserine dimers is mediated via activation of the Nrf2 signaling pathway vol.59, pp.2, 2015, https://doi.org/10.1002/mnfr.201400381
  43. Immunohistochemical Study of Nrf2-Antioxidant Response Element as Indicator of Oxidative Stress Induced by Cadmium in Developing Rats vol.2015, 2015, https://doi.org/10.1155/2015/570650
  44. Do glial cells play an anti-oxidative role in Huntington's disease? vol.48, pp.10, 2014, https://doi.org/10.3109/10715762.2014.936432
  45. Molecular effectors and modulators of hypericin-mediated cell death in bladder cancer cells vol.27, pp.13, 2008, https://doi.org/10.1038/sj.onc.1210825
  46. Redox regulation of antioxidant enzymes: post-translational modulation of catalase and glutathione peroxidase activity by resveratrol in diabetic rat liver vol.393, pp.1-2, 2014, https://doi.org/10.1007/s11010-014-2051-1
  47. Bisphenol A Increases BeWo Trophoblast Survival in Stress-Induced Paradigms through Regulation of Oxidative Stress and Apoptosis vol.28, pp.9, 2015, https://doi.org/10.1021/acs.chemrestox.5b00093
  48. Activation of the nuclear factor E2-related factor 2/anitioxidant response element alleviates the nitroglycerin-induced hyperalgesia in rats vol.17, pp.1, 2016, https://doi.org/10.1186/s10194-016-0694-x
  49. Walnuts (Seeds of Juglandis sinensis L.) Protect Human Epidermal Keratinocytes against UVB-Induced Mitochondria-Mediated Apoptosis through Upregulation of ROS Elimination Pathways vol.27, pp.3, 2014, https://doi.org/10.1159/000354917
  50. Sulforaphane enhances aquaporin-4 expression and decreases cerebral edema following traumatic brain injury vol.82, pp.4, 2005, https://doi.org/10.1002/jnr.20649
  51. A protective role of nuclear factor-erythroid 2-related factor-2 (Nrf2) in inflammatory disorders vol.690, pp.1-2, 2010, https://doi.org/10.1016/j.mrfmmm.2009.09.007
  52. Protective Effects of Hyperoside against Carbon Tetrachloride-Induced Liver Damage in Mice vol.74, pp.5, 2011, https://doi.org/10.1021/np200001x
  53. Chitosan prevents oxidative stress-induced amyloid β formation and cytotoxicity in NT2 neurons: involvement of transcription factors Nrf2 and NF-κB vol.337, pp.1-2, 2010, https://doi.org/10.1007/s11010-009-0284-1
  54. The crucial protective role of glutathione against tienilic acid hepatotoxicity in rats vol.232, pp.2, 2008, https://doi.org/10.1016/j.taap.2008.06.024
  55. Genetic Ablation of Nrf2 Enhances Susceptibility to Acute Lung Injury After Traumatic Brain Injury in Mice vol.234, pp.2, 2009, https://doi.org/10.3181/0807-RM-232
  56. Harmal Extract Induces Apoptosis of HCT116 Human Colon Cancer Cells, Mediated by Inhibition of Nuclear Factor-κB and Activator Protein-1 Signaling Pathways and Induction of Cytoprotective Genes vol.17, pp.4, 2016, https://doi.org/10.7314/APJCP.2016.17.4.1947
  57. Expression of NF-E2-related factor 2 (Nrf2) in the basilar artery after experimental subarachnoid hemorrhage in rabbits: A preliminary study vol.1358, 2010, https://doi.org/10.1016/j.brainres.2010.08.035
  58. Zinc protects against diabetes-induced pathogenic changes in the aorta: roles of metallothionein and nuclear factor (erythroid-derived 2)-like 2 vol.12, pp.1, 2013, https://doi.org/10.1186/1475-2840-12-54
  59. The protective effect of melatonin on smoke-induced vascular injury in rats and humans: a randomized controlled trial vol.60, pp.2, 2016, https://doi.org/10.1111/jpi.12305
  60. Protocatechuic acid induces antioxidant/detoxifying enzyme expression through JNK-mediated Nrf2 activation in murine macrophages vol.22, pp.5, 2011, https://doi.org/10.1016/j.jnutbio.2010.03.008
  61. Human fibroblast growth factor 20 (FGF-20; CG53135-05): A novel cytoprotectant with radioprotective potential vol.81, pp.8, 2005, https://doi.org/10.1080/09553000500211091
  62. Role of Kamut® brand khorasan wheat in the counteraction of non-celiac wheat sensitivity and oxidative damage vol.63, 2014, https://doi.org/10.1016/j.foodres.2014.01.065
  63. MicroRNA-206 induces G1 arrest in melanoma by inhibition of CDK4 and Cyclin D vol.27, pp.2, 2014, https://doi.org/10.1111/pcmr.12200
  64. Effects of multi-component mixtures of polyaromatic hydrocarbons and heavy metal/loid(s) on Nrf2-antioxidant response element (ARE) pathway in ARE reporter-HepG2 cells vol.5, pp.4, 2016, https://doi.org/10.1039/C6TX00024J
  65. The involvement of Nrf2 in the protective effects of diallyl disulfide on carbon tetrachloride-induced hepatic oxidative damage and inflammatory response in rats vol.63, 2014, https://doi.org/10.1016/j.fct.2013.11.006
  66. Resveratrol treatment restores peripheral insulin sensitivity in diabetic mice in a sirt1-independent manner vol.59, pp.8, 2015, https://doi.org/10.1002/mnfr.201400933
  67. Aging-related decline in the induction of Nrf2-regulated antioxidant genes in human bronchial epithelial cells vol.14, 2018, https://doi.org/10.1016/j.redox.2017.08.014
  68. Nrf2 Knockout Attenuates the Anti-Inflammatory Effects of Phenethyl Isothiocyanate and Curcumin vol.27, pp.12, 2014, https://doi.org/10.1021/tx500234h
  69. Physiological hepatic response to zinc oxide nanoparticle exposure in the white sucker, Catostomus commersonii vol.162, 2014, https://doi.org/10.1016/j.cbpc.2014.03.009
  70. Dietary Polyphenols as Modulators of Brain Functions: Biological Actions and Molecular Mechanisms Underpinning Their Beneficial Effects vol.2012, 2012, https://doi.org/10.1155/2012/914273
  71. Oroxylin A exerts anti-inflammatory activity on lipopolysaccharide-induced mouse macrophage via Nrf2/ARE activation vol.92, pp.5, 2014, https://doi.org/10.1139/bcb-2014-0030
  72. Dimethyl fumarate attenuates experimental autoimmune neuritis through the nuclear factor erythroid-derived 2-related factor 2/hemoxygenase-1 pathway by altering the balance of M1/M2 macrophages vol.13, pp.1, 2016, https://doi.org/10.1186/s12974-016-0559-x
  73. The novel antioxidant 3-O-caffeoyl-1-methylquinic acid induces Nrf2-dependent phase II detoxifying genes and alters intracellular glutathione redox vol.40, pp.8, 2006, https://doi.org/10.1016/j.freeradbiomed.2005.12.002
  74. Puerarin suppresses AGEs-induced inflammation in mouse mesangial cells: A possible pathway through the induction of heme oxygenase-1 expression vol.244, pp.2, 2010, https://doi.org/10.1016/j.taap.2009.12.023
  75. Aquaporins as targets of pharmacological plant-derived compounds vol.13, pp.3, 2014, https://doi.org/10.1007/s11101-013-9314-4
  76. Pterostilbene-mediated Nrf2 activation: Mechanistic insights on Keap1:Nrf2 interface vol.24, pp.16, 2016, https://doi.org/10.1016/j.bmc.2016.05.011
  77. Attenuation of NF-κB and activation of Nrf2 signaling by 1,2,4-triazine derivatives, protects neuron-like PC12 cells against apoptosis vol.15, pp.6, 2010, https://doi.org/10.1007/s10495-010-0496-6
  78. Natural Compounds as a Therapeutic Intervention following Traumatic Brain Injury: The Role of Phytochemicals vol.34, pp.8, 2017, https://doi.org/10.1089/neu.2016.4718
  79. Polyphénols et neuroprotection : où en sommes-nous aujourd’hui ? vol.49, pp.4, 2014, https://doi.org/10.1016/j.cnd.2014.01.001
  80. ROS production is required for follicle-stimulating hormone-induced Nrf2 activation in human epithelial ovarian cancer cells vol.32, pp.9, 2012, https://doi.org/10.3724/SP.J.1008.2012.00935
  81. Differential induction of electrophile-responsive element-regulated genes byn− 3 andn− 6 polyunsaturated fatty acids vol.580, pp.19, 2006, https://doi.org/10.1016/j.febslet.2006.07.028
  82. Emerging roles of system antiporter and its inhibition in CNS disorders vol.32, pp.4, 2015, https://doi.org/10.3109/09687688.2015.1096972
  83. Supplemental effects of probioticBacillus subtilisfmbJ on growth performance, antioxidant capacity, and meat quality of broiler chickens vol.96, pp.1, 2017, https://doi.org/10.3382/ps/pew246
  84. Sulforaphane suppresses LPS-induced inflammation in primary rat microglia vol.59, pp.6, 2010, https://doi.org/10.1007/s00011-009-0116-5
  85. Anti-inflammatory Effects of Amomum compactum on RAW 264.7 cells via induction of heme oxygenase-1 vol.35, pp.4, 2012, https://doi.org/10.1007/s12272-012-0419-x
  86. Deficient Glutathione in the Pathophysiology of Mycotoxin-Related Illness vol.6, pp.2, 2014, https://doi.org/10.3390/toxins6020608
  87. Chemopreventive functions and molecular mechanisms of garlic organosulfur compounds vol.5, pp.5, 2014, https://doi.org/10.1039/c3fo60479a
  88. Small Changes Huge Impact: The Role of Protein Posttranslational Modifications in Cellular Homeostasis and Disease vol.2011, 2011, https://doi.org/10.4061/2011/207691
  89. Potential mechanism of kaempferol against Cu2+-induced oxidative stress through chelating activity and regulation of nuclear factorerythroid-2-related factor 2 signaling vol.21, pp.5, 2012, https://doi.org/10.1007/s10068-012-0194-y
  90. Differential Dependence on Cysteine from TranssulfurationversusTransport During T Cell Activation vol.15, pp.1, 2011, https://doi.org/10.1089/ars.2010.3496
  91. Glia cell number modulates sensitivity to MPTP in mice vol.52, pp.2, 2005, https://doi.org/10.1002/glia.20233
  92. Phenylpropanoid glycosides from plant cell cultures induce heme oxygenase 1 gene expression in a human keratinocyte cell line by affecting the balance of NRF2 and BACH1 transcription factors vol.199, pp.2, 2012, https://doi.org/10.1016/j.cbi.2012.06.006
  93. Cytotoxicity of 1,4-diamino-2-butanone, a putrescine analogue, to RKO cells: mechanism and redox imbalance vol.47, pp.9, 2013, https://doi.org/10.3109/10715762.2013.814126
  94. ATF3 Protects Pulmonary Resident Cells from Acute and Ventilator-Induced Lung Injury by Preventing Nrf2 Degradation vol.22, pp.8, 2015, https://doi.org/10.1089/ars.2014.5987
  95. Bioactive Constituents ofGlycyrrhiza uralensis(Licorice): Discovery of the Effective Components of a Traditional Herbal Medicine vol.79, pp.2, 2016, https://doi.org/10.1021/acs.jnatprod.5b00877
  96. Combination of siRNA-directed gene silencing with epigallocatechin-3-gallate (EGCG) reverses drug resistance in human breast cancer cells vol.9, pp.1, 2016, https://doi.org/10.1007/s12154-015-0144-2
  97. GSTpi Expression in MPTP-Induced Dopaminergic Neurodegeneration of C57BL/6 Mouse Midbrain and Striatum vol.38, pp.2, 2009, https://doi.org/10.1007/s12031-008-9141-z
  98. 3-Hydroxykynurenine: An intriguing molecule exerting dual actions in the Central Nervous System vol.34, 2013, https://doi.org/10.1016/j.neuro.2012.11.007
  99. Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents vol.32, pp.4, 2012, https://doi.org/10.1002/med.21257
  100. Anti-H1N1 virus, cytotoxic and Nrf2 activation activities of chemical constituents from Scutellaria baicalensis vol.176, 2015, https://doi.org/10.1016/j.jep.2015.11.018
  101. Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injuryin vitroandin vivo vol.44, pp.10, 2014, https://doi.org/10.1111/hepr.12204
  102. Upregulation of genes orchestrating keratinocyte differentiation, including the novel marker geneID2, by contact sensitizers in human bulge-derived keratinocytes vol.24, pp.1, 2010, https://doi.org/10.1002/jbt.20307
  103. Activation of Nrf2-ARE signal pathway in hippocampus of amygdala kindling rats vol.543, 2013, https://doi.org/10.1016/j.neulet.2013.03.038
  104. Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model vol.53, pp.2, 2012, https://doi.org/10.1111/j.1600-079X.2012.00978.x
  105. The Anti-inflammatory Effect of Melatonin on Methamphetamine-Induced Proinflammatory Mediators in Human Neuroblastoma Dopamine SH-SY5Y Cell Lines vol.23, pp.2, 2013, https://doi.org/10.1007/s12640-012-9350-7
  106. Role of oxidative stress in the induction of metallothionein-2A and heme oxygenase-1 gene expression by the antineoplastic agent gallium nitrate in human lymphoma cells vol.45, pp.6, 2008, https://doi.org/10.1016/j.freeradbiomed.2008.05.031
  107. Omega-3 Polyunsaturated Fatty Acids Protect Neural Progenitor Cells against Oxidative Injury vol.12, pp.5, 2014, https://doi.org/10.3390/md12052341
  108. Mycophenolate mofetil and curcumin provide comparable therapeutic benefit in experimental chronic kidney disease: role of Nrf2-Keap1 and renal dopamine pathways vol.50, pp.7, 2016, https://doi.org/10.1080/10715762.2016.1174776
  109. PM2.5 induces Nrf2-mediated defense mechanisms against oxidative stress by activating PIK3/AKT signaling pathway in human lung alveolar epithelial A549 cells vol.29, pp.3, 2013, https://doi.org/10.1007/s10565-013-9242-5
  110. Increased intestinal inflammatory response and gut barrier dysfunction in Nrf2-deficient mice after traumatic brain injury vol.44, pp.1, 2008, https://doi.org/10.1016/j.cyto.2008.07.005
  111. The Nrf2–Keap1 cellular defense pathway and heat shock protein 70 (Hsp70) response. Role in protection against oxidative stress in early neonatal unilateral ureteral obstruction (UUO) vol.16, pp.1, 2011, https://doi.org/10.1007/s12192-010-0221-y
  112. Phorbaketal A, Isolated from the Marine Sponge Phorbas sp., Exerts Its Anti-Inflammatory Effects via NF-κB Inhibition and Heme Oxygenase-1 Activation in Lipopolysaccharide-Stimulated Macrophages vol.13, pp.12, 2015, https://doi.org/10.3390/md13117005
  113. Metformin inhibits 7,12-dimethylbenz[a]anthracene-induced breast carcinogenesis and adduct formation in human breast cells by inhibiting the cytochrome P4501A1/aryl hydrocarbon receptor signaling pathway vol.284, pp.2, 2015, https://doi.org/10.1016/j.taap.2015.02.007
  114. Effects of Tert-Butylhydroquinone on Intestinal Inflammatory Response and Apoptosis following Traumatic Brain Injury in Mice vol.2010, 2010, https://doi.org/10.1155/2010/502564
  115. Transcription Factor Nrf2 Protects the Spinal Cord from Inflammation Produced by Spinal Cord Injury vol.170, pp.1, 2011, https://doi.org/10.1016/j.jss.2011.05.049
  116. Inhibition of heme oxygenase-1 enhances the chemosensitivity of laryngeal squamous cell cancer Hep-2 cells to cisplatin vol.21, pp.4, 2016, https://doi.org/10.1007/s10495-016-1216-7
  117. Nrf2 Inhibits Periodontal Ligament Stem Cell Apoptosis under Excessive Oxidative Stress vol.18, pp.5, 2017, https://doi.org/10.3390/ijms18051076
  118. Coriandrum sativum L. Protects Human Keratinocytes from Oxidative Stress by Regulating Oxidative Defense Systems vol.25, pp.2, 2012, https://doi.org/10.1159/000335257
  119. Anti-oxidizing effect of the dichloromethane and hexane fractions from Orostachys japonicus in LPS-stimulated RAW 264.7 cells via upregulation of Nrf2 expression and activation of MAPK signaling pathway vol.47, pp.2, 2014, https://doi.org/10.5483/BMBRep.2014.47.2.088
  120. Small Maf Proteins in Mammalian Gene Control: Mere Dimerization Partners or Dynamic Transcriptional Regulators? vol.376, pp.4, 2008, https://doi.org/10.1016/j.jmb.2007.11.074
  121. Preclinical Studies and Translational Applications of Intracerebral Hemorrhage vol.2017, 2017, https://doi.org/10.1155/2017/5135429
  122. Berberine activates Nrf2 nuclear translocation and inhibits apoptosis induced by high glucose in renal tubular epithelial cells through a phosphatidylinositol 3-kinase/Akt-dependent mechanism vol.21, pp.6, 2016, https://doi.org/10.1007/s10495-016-1234-5
  123. Mitochondria, redox signaling and axis specification in metazoan embryos vol.308, pp.2, 2007, https://doi.org/10.1016/j.ydbio.2007.05.042
  124. Estrogen increases Nrf2 activity through activation of the PI3K pathway in MCF-7 breast cancer cells vol.328, pp.2, 2014, https://doi.org/10.1016/j.yexcr.2014.08.030
  125. Select cyclopentenone prostaglandins trigger glutathione efflux and the role of ABCG2 transport vol.47, pp.6, 2009, https://doi.org/10.1016/j.freeradbiomed.2009.06.005
  126. S-Glutathionylation of Keap1: a new role for glutathioneS-transferase pi in neuronal protection vol.590, pp.10, 2016, https://doi.org/10.1002/1873-3468.12177
  127. Disruption of Nrf2 Enhances Upregulation of Nuclear Factor-κB Activity, Proinflammatory Cytokines, and Intercellular Adhesion Molecule-1 in the Brain after Traumatic Brain Injury vol.2008, 2008, https://doi.org/10.1155/2008/725174
  128. Diterpenoids Isolated fromSideritisSpecies Protect Astrocytes against Oxidative Stress via Nrf2 vol.75, pp.10, 2012, https://doi.org/10.1021/np300418m
  129. Differential sensitivity to pro-oxidant exposure in two populations of killifish (Fundulus heteroclitus) vol.22, pp.2, 2013, https://doi.org/10.1007/s10646-012-1033-x
  130. Distal Airways in Mice Exposed to Cigarette Smoke vol.39, pp.4, 2008, https://doi.org/10.1165/rcmb.2007-0295OC
  131. Upregulation of heme oxygenase-1 expression by dehydrodiconiferyl alcohol (DHCA) through the AMPK–Nrf2 dependent pathway vol.281, pp.1, 2014, https://doi.org/10.1016/j.taap.2014.07.011
  132. Administration of red ginseng ameliorates memory decline in aged mice vol.39, pp.3, 2015, https://doi.org/10.1016/j.jgr.2015.01.003
  133. Acidosis-Induced Changes in Proteome Patterns of the Prostate Cancer-Derived Tumor Cell Line AT-1 vol.14, pp.9, 2015, https://doi.org/10.1021/acs.jproteome.5b00503
  134. Pathophysiological basis for the prophylaxis of preeclampsia through early supplementation with antioxidant vitamins vol.107, pp.2, 2005, https://doi.org/10.1016/j.pharmthera.2005.03.001
  135. Role of Nrf2 in Protection against Traumatic Brain Injury in Mice vol.26, pp.1, 2009, https://doi.org/10.1089/neu.2008.0655
  136. The dynamics of cysteine, glutathione and their disulphides in astrocyte culture medium vol.150, pp.1, 2011, https://doi.org/10.1093/jb/mvr038
  137. Age-related changes of Nrf2 and phosphorylated GSK-3β in a mouse model of accelerated aging (SAMP8) vol.54, pp.2, 2012, https://doi.org/10.1016/j.archger.2011.06.006
  138. Red Ginseng Extract Ameliorates Autoimmune Arthritis via Regulation of STAT3 Pathway, Th17/Treg Balance, and Osteoclastogenesis in Mice and Human vol.2014, 2014, https://doi.org/10.1155/2014/351856
  139. Natural products for cancer prevention associated with Nrf2–ARE pathway vol.2, pp.1, 2013, https://doi.org/10.1016/j.fshw.2013.01.001
  140. The anti-apoptotic effect of fucoxanthin on carbon tetrachloride-induced hepatotoxicity vol.38, pp.1, 2013, https://doi.org/10.2131/jts.38.115
  141. Testosterone Propionate Exacerbates the Deficits of Nigrostriatal Dopaminergic System and Downregulates Nrf2 Expression in Reserpine-Treated Aged Male Rats vol.9, 2017, https://doi.org/10.3389/fnagi.2017.00172
  142. Obesity increases cerebrocortical reactive oxygen species and impairs brainfunction vol.56, 2013, https://doi.org/10.1016/j.freeradbiomed.2012.08.577
  143. Silver nanoparticles down-regulate Nrf2-mediated 8-oxoguanine DNA glycosylase 1 through inactivation of extracellular regulated kinase and protein kinase B in human Chang liver cells vol.207, pp.2, 2011, https://doi.org/10.1016/j.toxlet.2011.09.002
  144. In vitro augmentation of mesenchymal stem cells viability in stressful microenvironments vol.20, pp.2, 2015, https://doi.org/10.1007/s12192-014-0560-1
  145. Chronic testosterone propionate supplement could activated the Nrf2-ARE pathway in the brain and ameliorated the behaviors of aged rats vol.252, 2013, https://doi.org/10.1016/j.bbr.2013.05.063
  146. Anthocyanins from fruit juices improve the antioxidant status of healthy young female volunteers without affecting anti-inflammatory parameters: results from the randomised, double-blind, placebo-controlled, cross-over ANTHONIA (ANTHOcyanins in Nutrition Investigation Alliance) study vol.112, pp.06, 2014, https://doi.org/10.1017/S0007114514001482
  147. Modulation of NAD(P)H:quinone oxidoreductase by vanadium in human hepatoma HepG2 cells vol.24, pp.6, 2010, https://doi.org/10.1016/j.tiv.2010.06.017
  148. Synthesis and Biological Activities of Neoechinulin A Derivatives: New Aspects of Structure–Activity Relationships for Neoechinulin A vol.56, pp.12, 2008, https://doi.org/10.1248/cpb.56.1738
  149. Sulforaphane Attenuation of Type 2 Diabetes-Induced Aortic Damage Was Associated with the Upregulation of Nrf2 Expression and Function vol.2014, 2014, https://doi.org/10.1155/2014/123963
  150. Omega-3 fatty acids and dementia vol.81, pp.2-3, 2009, https://doi.org/10.1016/j.plefa.2009.05.015
  151. Nrf2-ARE stress response mechanism: A control point in oxidative stress-mediated dysfunctions and chronic inflammatory diseases vol.44, pp.11, 2010, https://doi.org/10.3109/10715762.2010.507670
  152. Inhibition of JNK by compound C66 prevents pathological changes of the aorta in STZ-induced diabetes vol.18, pp.6, 2014, https://doi.org/10.1111/jcmm.12267
  153. Transcription Factor Nrf2 Plays a Pivotal Role in Protection Against Traumatic Brain Injury-Induced Acute Intestinal Mucosal Injury in Mice vol.157, pp.2, 2009, https://doi.org/10.1016/j.jss.2008.08.003
  154. Temozolomide and irradiation combined treatment-induced Nrf2 activation increases chemoradiation sensitivity in human glioblastoma cells vol.116, pp.1, 2014, https://doi.org/10.1007/s11060-013-1260-x
  155. Role of the Nrf2-ARE pathway in acrylamide neurotoxicity vol.205, pp.1, 2011, https://doi.org/10.1016/j.toxlet.2011.04.011
  156. Tea Catechins Protect Goat Skeletal Muscle against H2O2-Induced Oxidative Stress by Modulating Expression of Phase 2 Antioxidant Enzymes vol.63, pp.36, 2015, https://doi.org/10.1021/acs.jafc.5b00816
  157. Sulforaphane protects brains against hypoxic–ischemic injury through induction of Nrf2-dependent phase 2 enzyme vol.1343, 2010, https://doi.org/10.1016/j.brainres.2010.04.036
  158. Oxidative stress - a key emerging impact factor in health, ageing, lifestyle and aesthetics vol.37, 2015, https://doi.org/10.1111/ics.12287
  159. Hepatoprotective effects of S-adenosylmethionine and silybin on canine hepatocytesin vitro vol.97, pp.2, 2013, https://doi.org/10.1111/j.1439-0396.2012.01275.x
  160. Chemopreventive effects of Furan-2-yl-3-pyridin-2-yl-propenone against 7,12-dimethylbenz[a]anthracene-inducible genotoxicity vol.228, pp.3, 2008, https://doi.org/10.1016/j.taap.2007.12.018
  161. Role of Nrf2 in retinal vascular development and the vaso-obliterative phase of oxygen-induced retinopathy vol.90, pp.4, 2010, https://doi.org/10.1016/j.exer.2009.12.012
  162. Anti-inflammatory activity of xanthohumol involves heme oxygenase-1 induction via NRF2-ARE signaling in microglial BV2 cells vol.58, pp.2, 2011, https://doi.org/10.1016/j.neuint.2010.11.008
  163. MicroRNAs in erythropoiesis and red blood cell disorders vol.10, pp.4, 2015, https://doi.org/10.1007/s11515-015-1365-z
  164. Molecular mechanisms by which white tea prevents oxidative stress vol.70, pp.4, 2014, https://doi.org/10.1007/s13105-014-0357-9
  165. Song Bu Li Decoction, a Traditional Uyghur Medicine, Protects Cell Death by Regulation of Oxidative Stress and Differentiation in Cultured PC12 Cells vol.2013, 2013, https://doi.org/10.1155/2013/687958
  166. Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for hypoxic preconditioning-mediated delayed cardioprotection vol.385, pp.1-2, 2014, https://doi.org/10.1007/s11010-013-1812-6
  167. Characterization of the modes of action of deoxynivalenol (DON) in the human Jurkat T-cell line vol.12, pp.3, 2015, https://doi.org/10.3109/1547691X.2014.925995
  168. Expression of Nrf2 in Neurodegenerative Diseases vol.66, pp.1, 2007, https://doi.org/10.1097/nen.0b013e31802d6da9
  169. NARP mutation and mtDNA depletion trigger mitochondrial biogenesis which can be modulated by selenite supplementation vol.43, pp.8, 2011, https://doi.org/10.1016/j.biocel.2011.04.011
  170. Antioxidant and anti hyperglycemic role of wine grape powder in rats fed with a high fructose diet vol.48, pp.1, 2015, https://doi.org/10.1186/s40659-015-0045-4
  171. Oxidative stress in serum and peripheral blood leukocytes in patients with different disease courses of multiple sclerosis vol.253, pp.4, 2006, https://doi.org/10.1007/s00415-005-0037-3
  172. Sulforaphane enhances the activity of the Nrf2–ARE pathway and attenuates inflammation in OxyHb-induced rat vascular smooth muscle cells vol.62, pp.9, 2013, https://doi.org/10.1007/s00011-013-0641-0
  173. Mitochondrial dysfunction and oxidative damage in the molecular pathology of Parkinson’s disease vol.42, pp.5, 2008, https://doi.org/10.1134/S0026893308050099
  174. A Systems Toxicology Approach to Elucidate the Mechanisms Involved in RDX Species-Specific Sensitivity vol.46, pp.14, 2012, https://doi.org/10.1021/es300495c
  175. Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress vol.1637, 2016, https://doi.org/10.1016/j.brainres.2016.02.016
  176. Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2) Mediates Neuroprotection in Traumatic Brain Injury at Least in Part by Inactivating Microglia vol.22, 2016, https://doi.org/10.12659/MSM.896568
  177. Acute exposure to 3-methylcholanthrene induces hepatic oxidative stress via activation of the Nrf2/ARE signaling pathway in mice vol.29, pp.12, 2014, https://doi.org/10.1002/tox.21870
  178. The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer’s Disease vol.42, pp.1-2, 2007, https://doi.org/10.1016/j.exger.2006.08.009
  179. Epigallocatechin-3-Gallate Protects HUVECs from PM2.5-Induced Oxidative Stress Injury by Activating Critical Antioxidant Pathways vol.20, pp.4, 2015, https://doi.org/10.3390/molecules20046626
  180. Erythropoietin Administration Modulates Pulmonary Nrf2 Signaling Pathway After Traumatic Brain Injury in Mice vol.71, pp.3, 2011, https://doi.org/10.1097/TA.0b013e3181f6b984
  181. Location, Location, Location vol.66, pp.10, 2007, https://doi.org/10.1097/nen.0b013e318156a3d7
  182. Involvement of p-CREB and phase II detoxifying enzyme system in neuroprotection mediated by the flavonoid calycopterin isolated from Dracocephalum kotschyi vol.20, pp.10, 2013, https://doi.org/10.1016/j.phymed.2013.03.013
  183. Characterization of one typical 2-Cys Peroxiredoxin gene of Taenia solium and Taenia crassiceps vol.105, pp.3, 2009, https://doi.org/10.1007/s00436-009-1461-6
  184. Cancer chemoprevention: A radical perspective vol.45, pp.2, 2008, https://doi.org/10.1016/j.freeradbiomed.2008.04.004
  185. 15-Deoxy-Δ12,14-prostaglandin J2 rescues PC12 cells from H2O2-induced apoptosis through Nrf2-mediated upregulation of heme oxygenase-1: Potential roles of Akt and ERK1/2 vol.76, pp.11, 2008, https://doi.org/10.1016/j.bcp.2008.08.007
  186. Phytogenic Compounds as Alternatives to In-Feed Antibiotics: Potentials and Challenges in Application vol.4, pp.1, 2015, https://doi.org/10.3390/pathogens4010137
  187. Ozone-induced damage in 3D-Skin Model is prevented by topical vitamin C and vitamin E compound mixtures application vol.82, pp.3, 2016, https://doi.org/10.1016/j.jdermsci.2016.02.007
  188. Effects of Zn deficiency, antioxidants, and low-dose radiation on diabetic oxidative damage and cell death in the testis vol.23, pp.1, 2013, https://doi.org/10.3109/15376516.2012.731437
  189. Acute Phase Response of Selenium Status and Glutathione Peroxidase Activity in Blood Plasma Before and After Total Knee Arthroplasty Surgery vol.144, pp.1-3, 2011, https://doi.org/10.1007/s12011-011-9107-9
  190. Pyrroloquinoline quinone rescues hippocampal neurons from glutamate-induced cell death through activation of Nrf2 and up-regulation of antioxidant genes vol.11, pp.3, 2012, https://doi.org/10.4238/2012.June.27.3
  191. MicroRNAs: Allies or Foes in erythropoiesis? vol.227, pp.1, 2012, https://doi.org/10.1002/jcp.22729
  192. Docosahexaenoic Acid Induces Expression of Heme Oxygenase-1 and NAD(P)H:quinone Oxidoreductase through Activation of Nrf2 in Human Mammary Epithelial Cells vol.22, pp.6, 2017, https://doi.org/10.3390/molecules22060969
  193. Essential oils as alternatives to antibiotics in swine production 2017, https://doi.org/10.1016/j.aninu.2017.09.001
  194. Interplay between Nuclear Factor Erythroid 2–Related Factor 2 and Amphiregulin during Mechanical Ventilation vol.51, pp.5, 2014, https://doi.org/10.1165/rcmb.2013-0279OC
  195. Analysis of Pfizer Compounds in EPA’s ToxCast Chemicals-Assay Space vol.27, pp.1, 2014, https://doi.org/10.1021/tx400343t
  196. Thioredoxin and Cancer: A Role for Thioredoxin in all States of Tumor Oxygenation vol.2, pp.2, 2010, https://doi.org/10.3390/cancers2020209
  197. Nrf2 participates in depressive disorders through an anti-inflammatory mechanism vol.38, pp.10, 2013, https://doi.org/10.1016/j.psyneuen.2013.03.020
  198. The aryl hydrocarbon receptor: a perspective on potential roles in the immune system vol.127, pp.3, 2009, https://doi.org/10.1111/j.1365-2567.2009.03054.x
  199. Ebselen by modulating oxidative stress improves hypoxia-induced macroglial Müller cell and vascular injury in the retina vol.136, 2015, https://doi.org/10.1016/j.exer.2015.04.015
  200. Impact of Acetazolamide, a Carbonic Anhydrase Inhibitor, on the Development of Intestinal Polyps in Min Mice vol.18, pp.4, 2017, https://doi.org/10.3390/ijms18040851
  201. ROS and ROS-Mediated Cellular Signaling vol.2016, 2016, https://doi.org/10.1155/2016/4350965
  202. Downregulation of Glutathione Biosynthesis Contributes to Oxidative Stress and Liver Dysfunction in Acute Kidney Injury vol.2016, 2016, https://doi.org/10.1155/2016/9707292
  203. Paraquat induces lung alveolar epithelial cell apoptosis via Nrf-2-regulated mitochondrial dysfunction and ER stress vol.86, pp.10, 2012, https://doi.org/10.1007/s00204-012-0873-8
  204. Functional Aspects of Redox Control During Neuroinflammation vol.13, pp.2, 2010, https://doi.org/10.1089/ars.2009.2629
  205. Role of Nrf2-mediated heme oxygenase-1 upregulation in adaptive survival response to nitrosative stress vol.32, pp.8, 2009, https://doi.org/10.1007/s12272-009-1807-8
  206. A metabolomic perspective of griseofulvin-induced liver injury in mice vol.98, pp.3, 2015, https://doi.org/10.1016/j.bcp.2015.09.002
  207. Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician’s Expectation Be Matched by the Reality? vol.2016, 2016, https://doi.org/10.1155/2016/7857186
  208. Role of a fetal defence mechanism against oxidative stress in the aetiology of preeclampsia vol.55, pp.1, 2009, https://doi.org/10.1111/j.1365-2559.2009.03339.x
  209. Sulforaphane protects cortical neurons against 5-S-cysteinyl-dopamine-induced toxicity through the activation of ERK1/2, Nrf-2 and the upregulation of detoxification enzymes vol.54, pp.4, 2010, https://doi.org/10.1002/mnfr.200900197
  210. Copper and Myeloperoxidase-Modified LDLs Activate Nrf2 Through Different Pathways of ROS Production in Macrophages vol.13, pp.10, 2010, https://doi.org/10.1089/ars.2009.2971
  211. Cell defense systems against oxidative stress and endoplasmic reticulum stress: Mechanisms of regulation and the effect of hepatitis C virus vol.45, pp.1, 2011, https://doi.org/10.1134/S0026893311010122
  212. Cap-independent Nrf2 translation is part of a lipoic acid-stimulated detoxification stress response vol.1823, pp.6, 2012, https://doi.org/10.1016/j.bbamcr.2012.04.002
  213. Lipoic acid and pentoxifylline mitigate nandrolone decanoate-induced neurobehavioral perturbations in rats via re-balance of brain neurotransmitters, up-regulation of Nrf2/HO-1 pathway, and down-regulation of TNFR1 expression vol.73, 2015, https://doi.org/10.1016/j.yhbeh.2015.07.007
  214. Activation of Nrf2 by cadmium and its role in protection against cadmium-induced apoptosis in rat kidney cells vol.241, pp.1, 2009, https://doi.org/10.1016/j.taap.2009.07.038
  215. Nrf2 regulates hyperoxia-induced Nox4 expression in human lung endothelium: Identification of functional antioxidant response elements on the Nox4 promoter vol.50, pp.12, 2011, https://doi.org/10.1016/j.freeradbiomed.2011.03.022
  216. Glutathione antioxidant pathway activity and reserve determine toxicity and specificity of the biliary toxin biliatresone in zebrafish vol.64, pp.3, 2016, https://doi.org/10.1002/hep.28603
  217. Utilization of the Ability to Induce Activation of the Nuclear Factor (Erythroid-derived 2)-like Factor 2 (Nrf2) to Assess Potential Cancer Chemopreventive Activity of Liquorice Samples vol.27, pp.5, 2016, https://doi.org/10.1002/pca.2616
  218. The xc− cystine/glutamate antiporter: A potential target for therapy of cancer and other diseases vol.215, pp.3, 2008, https://doi.org/10.1002/jcp.21366
  219. Schisandrin B exhibits anti-inflammatory activity through modulation of the redox-sensitive transcription factors Nrf2 and NF-κB vol.53, pp.7, 2012, https://doi.org/10.1016/j.freeradbiomed.2012.08.006
  220. Glutathione S-transferase P1-1 as a target for mesothelioma treatment vol.104, pp.2, 2013, https://doi.org/10.1111/cas.12061
  221. Exacerbation of diabetes-induced testicular apoptosis by zinc deficiency is most likely associated with oxidative stress, p38 MAPK activation, and p53 activation in mice vol.200, pp.1-2, 2011, https://doi.org/10.1016/j.toxlet.2010.11.001
  222. Hepatoprotective effects of soluble rice protein in primary hepatocytes and in mice vol.96, pp.2, 2016, https://doi.org/10.1002/jsfa.7153
  223. The role of rhynchophylline in alleviating early brain injury following subarachnoid hemorrhage in rats vol.1631, 2016, https://doi.org/10.1016/j.brainres.2015.11.035
  224. Induction of Nrf2-mediated cellular defenses and alteration of phase I activities as mechanisms of chemoprotective effects of coffee in the liver vol.46, pp.4, 2008, https://doi.org/10.1016/j.fct.2007.09.099
  225. Antioxidant and Vasodilator Activity ofUgni molinaeTurcz. (Murtilla) and Its Modulatory Mechanism in Hypotensive Response vol.2016, 2016, https://doi.org/10.1155/2016/6513416
  226. Role of reactive oxygen species in modulation of Nrf2 following ischemic reperfusion injury vol.147, pp.1, 2007, https://doi.org/10.1016/j.neuroscience.2007.02.066
  227. Nrf2 defense pathway: Experimental evidence for its protective role in epilepsy vol.74, pp.4, 2013, https://doi.org/10.1002/ana.23940
  228. Induction of antioxidant and detoxification response by oxidants in cardiomyocytes: Evidence from gene expression profiling and activation of Nrf2 transcription factor vol.42, pp.1, 2007, https://doi.org/10.1016/j.yjmcc.2006.09.012
  229. Effects of phytochemicals on ionization radiation-mediated carcinogenesis and cancer therapy vol.728, pp.3, 2011, https://doi.org/10.1016/j.mrrev.2011.07.005
  230. A Review of the Use of Melatonin in Ulcerative Colitis vol.20, pp.3, 2014, https://doi.org/10.1097/01.MIB.0000436962.32164.6e
  231. CYP1A1, CYP1A2 and CYBA gene polymorphisms associated with oxidative stress in COPD vol.411, pp.7-8, 2010, https://doi.org/10.1016/j.cca.2009.12.018
  232. Chemopreventive role of anthocyanins in atherosclerosis via activation of Nrf2–ARE as an indicator and modulator of redox vol.72, 2015, https://doi.org/10.1016/j.biopha.2015.03.008
  233. Increased nuclear factor-erythroid 2 p45-related factor 2 activity protects SH-SY5Y cells against oxidative damage vol.95, pp.2, 2005, https://doi.org/10.1111/j.1471-4159.2005.03377.x
  234. Anti-Inflammatory Therapy Modulates Nrf2-Keap1 in Kidney from Rats with Diabetes vol.2016, 2016, https://doi.org/10.1155/2016/4693801
  235. Oxidative damage of lung and its protective mechanism in mice caused by long-term exposure to titanium dioxide nanoparticles vol.100A, pp.10, 2012, https://doi.org/10.1002/jbm.a.34190
  236. Sulforaphane: translational research from laboratory bench to clinic vol.71, pp.11, 2013, https://doi.org/10.1111/nure.12060
  237. Sulforaphane reduces infarct volume following focal cerebral ischemia in rodents vol.393, pp.2-3, 2006, https://doi.org/10.1016/j.neulet.2005.09.065
  238. A Chemically Standardized Extract ofZiziphus jujubaFruit (Jujube) Stimulates Expressions of Neurotrophic Factors and Anti-oxidant Enzymes in Cultured Astrocytes vol.28, pp.11, 2014, https://doi.org/10.1002/ptr.5202
  239. Protopanaxatriol Ginsenoside Rh1 Upregulates Phase II Antioxidant Enzyme Gene Expression in Rat Primary Astrocytes: Involvement of MAP Kinases and Nrf2/ARE Signaling vol.24, pp.1, 2016, https://doi.org/10.4062/biomolther.2015.129
  240. Zearalenone induces oxidative damage involving Keap1/Nrf2/HO-1 pathway in hepatic L02 cells vol.10, pp.4, 2014, https://doi.org/10.1007/s13273-014-0050-7
  241. Potential Chemoprevention Activity of Pterostilbene by Enhancing the Detoxifying Enzymes in the HT-29 Cell Line vol.13, pp.12, 2012, https://doi.org/10.7314/APJCP.2012.13.12.6403
  242. Pterostilbene Ameliorates Streptozotocin-Induced Diabetes through Enhancing Antioxidant Signaling Pathways Mediated by Nrf2 vol.29, pp.1, 2016, https://doi.org/10.1021/acs.chemrestox.5b00378
  243. Role of Nrf2 signaling in regulation of antioxidants and phase 2 enzymes in cardiac fibroblasts: Protection against reactive oxygen and nitrogen species-induced cell injury vol.579, pp.14, 2005, https://doi.org/10.1016/j.febslet.2005.04.058
  244. NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training vol.99, pp.5, 2005, https://doi.org/10.1152/japplphysiol.00380.2005
  245. Reoxygenation-specific activation of the antioxidant transcription factor Nrf2 mediates cytoprotective gene expression in ischemia-reperfusion injury vol.20, pp.14, 2006, https://doi.org/10.1096/fj.06-5097fje
  246. Models for the study of skin wound healing. The role of Nrf2 and NF-κB vol.161, pp.1, 2017, https://doi.org/10.5507/bp.2016.063
  247. Metabolic Responses in Endothelial Cells Following Exposure to Ketone Bodies vol.10, pp.2, 2018, https://doi.org/10.3390/nu10020250
  248. E-p-Methoxycinnamoyl-α-l-rhamnopyranosyl Ester, a Phenylpropanoid Isolated from Scrophularia buergeriana, Increases Nuclear Factor Erythroid-Derived 2-Related Factor 2 Stability by Inhibiting Ubiquitination in Human Keratinocytes vol.23, pp.4, 2018, https://doi.org/10.3390/molecules23040768
  249. Spleen tyrosine kinase-dependent Nrf2 activation regulates oxidative stress-induced cell death in WiL2-NS human B lymphoblasts pp.1029-2470, 2018, https://doi.org/10.1080/10715762.2018.1505044
  250. A Chinese Herbal Preparation, Xiao-Er-An-Shen Decoction, Exerts Neuron Protection by Modulation of Differentiation and Antioxidant Activity in Cultured PC12 Cells vol.2018, pp.1741-4288, 2018, https://doi.org/10.1155/2018/8670421
  251. Astaxanthin Promotes Nrf2/ARE Signaling to Inhibit HG-Induced Renal Fibrosis in GMCs vol.16, pp.4, 2018, https://doi.org/10.3390/md16040117
  252. Activation of Nrf2/ARE pathway alleviates the cognitive deficits in PS1V97L‐Tg mouse model of Alzheimer’s disease through modulation of oxidative stress vol.97, pp.4, 2019, https://doi.org/10.1002/jnr.24357
  253. Protective effects of ethyl gallate on H2O2-induced mitochondrial dysfunction in PC12 cells pp.1573-7365, 2019, https://doi.org/10.1007/s11011-019-0382-z
  254. Deciphering the Nutraceutical Potential of Raphanus sativus—A Comprehensive Overview vol.11, pp.2, 2019, https://doi.org/10.3390/nu11020402
  255. HEK293 Cells Overexpressing Nuclear Factor E2-Related Factor-2 Improve Expression of Recombinant Coagulation Factor VII pp.1559-0305, 2019, https://doi.org/10.1007/s12033-019-00160-y