Nrf2 protects against airway disorders

Toxicology and Applied Pharmacology

Volumn 244, Issue 1, 2010, Pages 43-56

  Cho, Hye Youn ^a   Kleeberger, Steven R ^a  

^a NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES   (United States)

Author keywords

ARE; Keap1; Knockout mice; Lung; Mutation; Oxidant; Polymorphism

Indexed keywords

ACTIN; ALPHA 1 ANTITRYPSIN; ALPHA TOCOPHEROL; ALPHA4 INTEGRIN; ALPHA5 INTEGRIN; AQUAPORIN; AQUAPORIN 1; BLEOMYCIN; CARBONYL REDUCTASE; CATALASE; CATHEPSIN S; CCAAT BINDING FACTOR; EARLY GROWTH RESPONSE FACTOR 1; ESTERASE; GLUTATHIONE TRANSFERASE A1; GLUTATHIONE TRANSFERASE M1; GROWTH ARREST AND DNA DAMAGE INDUCIBLE PROTEIN 45; HEME OXYGENASE 1; HEXOKINASE; INTERLEUKIN 6; KELCH LIKE ECH ASSOCIATED PROTEIN 1; PLATELET DERIVED GROWTH FACTOR B; PROTEIN TYROSINE PHOSPHATASE; SMAD3 PROTEIN; SUPEROXIDE DISMUTASE; THIOREDOXIN REDUCTASE 1; TRANSCRIPTION FACTOR NRF2; TUMOR NECROSIS FACTOR ALPHA; UBIQUITIN C;

ACUTE LUNG INJURY; ADULT RESPIRATORY DISTRESS SYNDROME; ANTIOXIDANT RESPONSIVE ELEMENT; APOPTOSIS; ARTIFICIAL VENTILATION; CELL CYCLE REGULATION; CHRONIC OBSTRUCTIVE LUNG DISEASE; EMPHYSEMA; EPIGENETICS; HUMAN; HYPEROXIA; INTERSTITIAL PNEUMONIA; LIPID PEROXIDATION; LUNG CANCER; LUNG FIBROSIS; MICROARRAY ANALYSIS; NONHUMAN; OXIDATIVE STRESS; PROMOTER REGION; PROTEIN EXPRESSION; PROTEIN FUNCTION; RESPIRATORY TRACT DISEASE; REVIEW; SEPSIS; SINGLE NUCLEOTIDE POLYMORPHISM; TIDAL VOLUME;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; BINDING SITES; CYTOSKELETAL PROTEINS; GENE EXPRESSION REGULATION; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LUNG; LUNG DISEASES; MICE; MICE, KNOCKOUT; NF-E2-RELATED FACTOR 2; OXIDATIVE STRESS; RESPONSE ELEMENTS; SIGNAL TRANSDUCTION;

BACTERIA (MICROORGANISMS); MUS;

EID: 77649273792     PISSN: 0041008X     EISSN: 10960333     Source Type: Journal    
DOI: 10.1016/j.taap.2009.07.024     Document Type: Review

References (183)

1. Adair-Kirk T.L., Atkinson J.J., Griffin G.L., Watson M.A., Kelley D.G., DeMello D., Senior R.M., and Betsuyaku T. Distal airways in mice exposed to cigarette smoke: Nrf2-regulated genes are increased in Clara cells. Am. J. Respir. Cell Mol. Biol. 39 (2008) 400-411
2. Aleyasin H., Rousseaux M.W., Phillips M., Kim R.H., Bland R.J., Callaghan S., Slack R.S., During M.J., Mak T.W., and Park D.S. The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 18748-18753
3. Angus D.C., Linde-Zwirble W.T., Lidicker J., Clermont G., Carcillo J., and Pinsky M.R. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit. Care Med. 29 (2001) 1303-1310
4. Aoki Y., Sato H., Nishimura N., Takahashi S., Itoh K., and Yamamoto M. Accelerated DNA adduct formation in the lung of the Nrf2 knockout mouse exposed to diesel exhaust. Toxicol. Appl. Pharmacol. 173 (2001) 154-160
5. Arisawa T., Tahara T., Shibata T., Nagasaka M., Nakamura M., Kamiya Y., Fujita H., Yoshioka D., Arima Y., Okubo M., Hirata I., and Nakano H. The influence of promoter polymorphism of nuclear factor-erythroid 2-related factor 2 gene on the aberrant DNA methylation in gastric epithelium. Oncol. Report. 19 (2008) 211-216
6. Asikainen T.M., Huang T.T., Taskinen E., Levonen A.L., Carlson E., Lapatto R., Epstein C.J., and Raivio K.O. Increased sensitivity of homozygous Sod2 mutant mice to oxygen toxicity. Free Radic. Biol. Med. 32 (2002) 175-186
7. Asikainen T.M., and White C.W. Pulmonary antioxidant defenses in the preterm newborn with respiratory distress and bronchopulmonary dysplasia in evolution: implications for antioxidant therapy. Antioxid. Redox Signal. 6 (2004) 155-167
8. Bakin A.V., Stourman N.V., Sekhar K.R., Rinehart C., Yan X., Meredith M.J., Arteaga C.L., and Freeman M.L. Smad3-ATF3 signaling mediates TGF-beta suppression of genes encoding Phase II detoxifying proteins. Free Radic. Biol. Med. 38 (2005) 375-387
9. Baraldi E., and Filippone M. Chronic lung disease after premature birth. N. Engl. J. Med. 357 (2007) 1946-1955
10. Barrios R., Shi Z.Z., Kala S.V., Wiseman A.L., Welty S.E., Kala G., Bahler A.A., Ou C.N., and Lieberman M.W. Oxygen-induced pulmonary injury in gamma-glutamyl transpeptidase-deficient mice. Lung 179 (2001) 319-330
11. Becker Y. Respiratory syncytial virus (RSV) evades the human adaptive immune system by skewing the Th1/Th2 cytokine balance toward increased levels of Th2 cytokines and IgE, markers of allergy-a review. Virus Genes 33 (2006) 235-252
12. Beeh K.M., Beier J., Haas I.C., Kornmann O., Micke P., and Buhl R. Glutathione deficiency of the lower respiratory tract in patients with idiopathic pulmonary fibrosis. Eur. Respir. J. 19 (2002) 1119-1123
13. Behera A.K., Matsuse H., Kumar M., Kong X., Lockey R.F., and Mohapatra S.S. Blocking intercellular adhesion molecule-1 on human epithelial cells decreases respiratory syncytial virus infection. Biochem. Biophys. Res. Commun. 280 (2001) 188-195
14. Bland R.D. Neonatal chronic lung disease in the post-surfactant era. Biol. Neonate 88 (2005) 181-191
15. Boelen A., Kwakkel J., Barends M., de Rond L., Dormans J., and Kimman T. Effect of lack of Interleukin-4, Interleukin-12, Interleukin-18, or the Interferon-gamma receptor on virus replication, cytokine response, and lung pathology during respiratory syncytial virus infection in mice. J. Med. Virol. 66 (2002) 552-560
16. Bowler R.P., Nicks M., Warnick K., and Crapo J.D. Role of extracellular superoxide dismutase in bleomycin-induced pulmonary fibrosis. Am. J. Physiol. Lung Cell Mol. Physiol. 282 (2002) L719-726
17. Canada A.T., Herman L.A., and Young S.L. An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms. Am. J. Physiol. 268 (1995) L539-545
18. Cantin A.M., North S.L., Fells G.A., Hubbard R.C., and Crystal R.G. Oxidant-mediated epithelial cell injury in idiopathic pulmonary fibrosis. J. Clin. Invest. 79 (1987) 1665-1673
19. Casola A., Burger N., Liu T., Jamaluddin M., Brasier A.R., and Garofalo R.P. Oxidant tone regulates RANTES gene expression in airway epithelial cells infected with respiratory syncytial virus. Role in viral-induced interferon regulatory factor activation. J. Biol. Chem. 276 (2001) 19715-19722
20. Castro S.M., Guerrero-Plata A., Suarez-Real G., Adegboyega P.A., Colasurdo G.N., Khan A.M., Garofalo R.P., and Casola A. Antioxidant treatment ameliorates respiratory syncytial virus-induced disease and lung inflammation. Am. J. Respir. Crit. Care Med. 174 (2006) 1361-1369
21. Chan J.Y., and Kwong M. Impaired expression of glutathione synthetic enzyme genes in mice with targeted deletion of the Nrf2 basic-leucine zipper protein. Biochim. Biophys. Acta 1517 (2000) 19-26
22. Chan K., and Kan Y.W. Nrf2 is essential for protection against acute pulmonary injury in mice. Proc. Natl. Acad. Sci. U. S. A. 96 (1999) 12731-12736
23. Cho H.Y., Imani F., Miller-DeGraff L., Walters D., Melendi G.A., Yamamoto M., Polack F.P., and Kleeberger S.R. Antiviral activity of Nrf2 in a murine model of respiratory syncytial virus disease. Am. J. Respir. Crit. Care Med. 179 (2009) 138-150
24. Cho H.Y., Jedlicka A.E., Reddy S.P., Kensler T.W., Yamamoto M., Zhang L.Y., and Kleeberger S.R. Role of NRF2 in protection against hyperoxic lung injury in mice. Am. J. Respir. Cell Mol. Biol. 26 (2002) 175-182
25. Cho H.Y., Jedlicka A.E., Reddy S.P., Zhang L.Y., Kensler T.W., and Kleeberger S.R. Linkage analysis of susceptibility to hyperoxia. Nrf2 is a candidate gene. Am. J. Respir. Cell Mol. Biol. 26 (2002) 42-51
26. Cho H.Y., Reddy S.P., Yamamoto M., and Kleeberger S.R. The transcription factor NRF2 protects against pulmonary fibrosis. Faseb J. 18 (2004) 1258-1260
27. Cho H.Y., Reddy S.P., Debiase A., Yamamoto M., and Kleeberger S.R. Gene expression profiling of NRF2-mediated protection against oxidative injury. Free Radic. Biol. Med. 38 (2005) 325-343
28. Clements C.M., McNally R.S., Conti B.J., Mak T.W., and Ting J.P. DJ-1, a cancer- and Parkinson's disease-associated protein, stabilizes the antioxidant transcriptional master regulator Nrf2. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 15091-15096
29. Cohen J. The immunopathogenesis of sepsis. Nature 420 (2002) 885-891
30. Cortijo J., Cerda-Nicolas M., Serrano A., Bioque G., Estrela J.M., Santangelo F., Esteras A., Llombart-Bosch A., and Morcillo E.J. Attenuation by oral N-acetylcysteine of bleomycin-induced lung injury in rats. Eur. Respir. J. 17 (2001) 1228-1235
31. Crapo J.D. Morphologic changes in pulmonary oxygen toxicity. Annu. Rev. Physiol. 48 (1986) 721-731
32. Crapo J.D., Barry B.E., Chang L.Y., and Mercer R.R. Alterations in lung structure caused by inhalation of oxidants. J. Toxicol. Environ. Health 13 (1984) 301-321
33. Danel C., Erzurum S.C., Prayssac P., Eissa N.T., Crystal R.G., Herve P., Baudet B., Mazmanian M., and Lemarchand P. Gene therapy for oxidant injury-related diseases: adenovirus-mediated transfer of superoxide dismutase and catalase cDNAs protects against hyperoxia but not against ischemia-reperfusion lung injury. Hum. Gene Ther. 9 (1998) 1487-1496
34. Deger Y., Yur F., Ertekin A., Mert N., Dede S., and Mert H. Protective effect of alpha-tocopherol on oxidative stress in experimental pulmonary fibrosis in rats. Cell Biochem. Funct. 25 (2007) 633-637
35. Denu J.M., and Tanner K.G. Specific and reversible inactivation of protein tyrosine phosphatases by hydrogen peroxide: evidence for a sulfenic acid intermediate and implications for redox regulation. Biochemistry 37 (1998) 5633-5642
36. Devling T.W., Lindsay C.D., McLellan L.I., McMahon M., and Hayes J.D. Utility of siRNA against Keap1 as a strategy to stimulate a cancer chemopreventive phenotype. Proc. Natl. Acad. Sci. U. S. A. 102 (2005) 7280-7285A
37. Dhakshinamoorthy S., and Jaiswal A.K. Functional characterization and role of INrf2 in antioxidant response element-mediated expression and antioxidant induction of NAD(P)H:quinone oxidoreductase1 gene. Oncogene 20 (2001) 3906-3917
38. Dinkova-Kostova A.T., Holtzclaw W.D., Cole R.N., Itoh K., Wakabayashi N., Katoh Y., Yamamoto M., and Talalay P. . Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 11908-11913
39. Erickson A.M., Nevarea Z., Gipp J.J., and Mulcahy R.T. Identification of a variant antioxidant response element in the promoter of the human glutamate-cysteine ligase modifier subunit gene. Revision of the ARE consensus sequence. J. Biol. Chem. 277 (2002) 30730-30737
40. Fahey J.W., and Talalay P. Antioxidant functions of sulforaphane: a potent inducer of Phase II detoxication enzymes. Food Chem. Toxicol. 37 (1999) 973-979
41. Fahey J.W., Haristoy X., Dolan P.M., Kensler T.W., Scholtus I., Stephenson K.K., Talalay P., and Lozniewski A. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc. Natl. Acad. Sci. U.S.A. 99 (2002) 7610-7615
42. Fattman C.L., Chang L.Y., Termin T.A., Petersen L., Enghild J.J., and Oury T.D. Enhanced bleomycin-induced pulmonary damage in mice lacking extracellular superoxide dismutase. Free Radic. Biol. Med. 35 (2003) 763-771
43. Folz R.J., Abushamaa A.M., and Suliman H.B. Extracellular superoxide dismutase in the airways of transgenic mice reduces inflammation and attenuates lung toxicity following hyperoxia. J. Clin. Invest. 103 (1999) 1055-1066
44. Foy H.M., Cooney M.K., Maletzky A.J., and Grayston J.T. Incidence and etiology of pneumonia, croup and bronchiolitis in preschool children belonging to a prepaid medical care group over a four-year period. Am. J. Epidemiol. 97 (1973) 80-92
45. Fracica P.J., Knapp M.J., and Crapo J.D. Patterns of progression and markers of lung injury in rodents and subhuman primates exposed to hyperoxia. Exp. Lung Res. 14 Suppl. (1988) 869-885
46. Fridovich I. Oxygen toxicity: a radical explanation. J. Exp. Biol. 201 Pt. 8 (1998) 1203-1209
47. Furukawa M., and Xiong Y. BTB protein Keap1 targets antioxidant transcription factor Nrf2 for ubiquitination by the Cullin 3-Roc1 ligase. Mol. Cell. Biol. 25 (2005) 162-171
48. Gebel S., Gerstmayer B., Bosio A., Haussmann H.J., Van Miert E., and Muller T. Gene expression profiling in respiratory tissues from rats exposed to mainstream cigarette smoke. Carcinogenesis 25 (2004) 169-178
49. Gerhauser C., You M., Liu J., Moriarty R.M., Hawthorne M., Mehta R.G., Moon R.C., and Pezzuto J.M. Cancer chemopreventive potential of sulforamate, a novel analogue of sulforaphane that induces phase 2 drug-metabolizing enzymes. Cancer Res. 57 (1997) 272-278
50. Goss C.H., Brower R.G., Hudson L.D., and Rubenfeld G.D. Incidence of acute lung injury in the United States. Crit. Care Med. 31 (2003) 1607-1611
51. Hackett N.R., Heguy A., Harvey B.G., O'Connor T.P., Luettich K., Flieder D.B., Kaplan R., and Crystal R.G. Variability of antioxidant-related gene expression in the airway epithelium of cigarette smokers. Am. J. Respir. Cell Mol. Biol. 29 (2003) 331-343
52. Hall C.B. Respiratory syncytial virus: a continuing culprit and conundrum. J. Pediatr. 135 (1999) 2-7
53. Halliwell B., Gutteridge J.M., and Cross C.E. Free radicals, antioxidants, and human disease: where are we now?. J. Lab. Clin. Med. 119 (1992) 598-620
54. Hayashi A., Suzuki H., Itoh K., Yamamoto M., and Sugiyama Y. Transcription factor Nrf2 is required for the constitutive and inducible expression of multidrug resistance-associated protein 1 in mouse embryo fibroblasts. Biochem. Biophys. Res. Commun. 310 (2003) 824-829
55. Hayes J.D., and McMahon M. NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem. Sci. 34 (2009) 176-188
56. He L.S., Chang S.W., Ortiz de Montellano P., Burke T.J., and Voelkel N.F. Lung injury in Fischer but not Sprague-Dawley rats after short-term hyperoxia. Am. J. Physiol. 259 (1990) L451-458
57. He C.H., Gong P., Hu B., Stewart D., Choi M.E., Choi A.M., and Alam J. Identification of activating transcription factor 4 (ATF4) as an Nrf2-interacting protein. Implication for heme oxygenase-1 gene regulation. J. Biol. Chem. 276 (2001) 20858-20865
58. Hirota K., Nakamura H., Masutani H., and Yodoi J. Thioredoxin superfamily and thioredoxin-inducing agents. Ann. N.Y. Acad. Sci. 957 (2002) 189-199
59. Ho Y.S., Vincent R., Dey M.S., Slot J.W., and Crapo J.D. Transgenic models for the study of lung antioxidant defense: enhanced manganese-containing superoxide dismutase activity gives partial protection to B6C3 hybrid mice exposed to hyperoxia. Am. J. Respir. Cell Mol. Biol. 18 (1998) 538-547
60. Hoshino T., Nakamura H., Okamoto M., Kato S., Araya S., Nomiyama K., Oizumi K., Young H.A., Aizawa H., and Yodoi J. Redox-active protein thioredoxin prevents proinflammatory cytokine- or bleomycin-induced lung injury. Am. J. Respir. Crit. Care Med. 168 (2003) 1075-1083
61. Hudak B.B., Zhang L.Y., and Kleeberger S.R. Inter-strain variation in susceptibility to hyperoxic injury of murine airways. Pharmacogenetics 3 (1993) 135-143
62. Iida K., Itoh K., Kumagai Y., Oyasu R., Hattori K., Kawai K., Shimazui T., Akaza H., and Yamamoto M. Nrf2 is essential for the chemopreventive efficacy of oltipraz against urinary bladder carcinogenesis. Cancer Res. 64 (2004) 6424-6431
63. Iizuka T., Ishii Y., Itoh K., Kiwamoto T., Kimura T., Matsuno Y., Morishima Y., Hegab A.E., Homma S., Nomura A., Sakamoto T., Shimura M., Yoshida A., Yamamoto M., and Sekizawa K. Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema. Genes Cells 10 (2005) 1113-1125
64. Inden M., Taira T., Kitamura Y., Yanagida T., Tsuchiya D., Takata K., Yanagisawa D., Nishimura K., Taniguchi T., Kiso Y., Yoshimoto K., Agatsuma T., Koide-Yoshida S., Iguchi-Ariga S.M., Shimohama S., and Ariga H. PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model. Neurobiol. Dis. 24 (2006) 144-158
65. Ishida R., and Takahashi T. Increased DNA chain breakage by combined action of bleomycin and superoxide radical. Biochem. Biophys. Res. Commun. 66 (1975) 1432-1438
66. Ishii T., Itoh K., Sato H., and Bannai S. Oxidative stress-inducible proteins in macrophages. Free Radic. Res. 31 (1999) 351-355
67. Ishii T., Itoh K., Ruiz E., Leake D.S., Unoki H., Yamamoto M., and Mann G.E. Role of Nrf2 in the regulation of CD36 and stress protein expression in murine macrophages: activation by oxidatively modified LDL and 4-hydroxynonenal. Circ. Res. 94 (2004) 609-616
68. Ishii Y., Itoh K., Morishima Y., Kimura T., Kiwamoto T., Iizuka T., Hegab A.E., Hosoya T., Nomura A., Sakamoto T., Yamamoto M., and Sekizawa K. Transcription factor Nrf2 plays a pivotal role in protection against elastase-induced pulmonary inflammation and emphysema. J. Immunol. 175 (2005) 6968-6975
69. 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. An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem. Biophys. Res. Commun. 236 (1997) 313-322
70. Itoh K., Ishii T., Wakabayashi N., and Yamamoto M. Regulatory mechanisms of cellular response to oxidative stress. Free Radic. Res. 31 (1999) 319-324
71. Itoh K., Wakabayashi N., Katoh Y., Ishii T., O'Connor T., and Yamamoto M. Keap1 regulates both cytoplasmic-nuclear shuttling and degradation of Nrf2 in response to electrophiles. Genes Cells 8 (2003) 379-391
72. Itoh K., Tong K.I., and Yamamoto M. Molecular mechanism activating Nrf2-Keap1 pathway in regulation of adaptive response to electrophiles. Free Radic. Biol. Med. 36 (2004) 1208-1213
73. Jardine H., MacNee W., Donaldson K., and Rahman I. . Molecular mechanism of transforming growth factor (TGF)-beta1-induced glutathione depletion in alveolar epithelial cells. Involvement of AP-1/ARE and Fra-1. J. Biol. Chem. 277 (2002) 21158-21166
74. Jean J.C., Liu Y., Brown L.A., Marc R.E., Klings E., and Joyce-Brady M. Gamma-glutamyl transferase deficiency results in lung oxidant stress in normoxia. Am. J. Physiol., Lung Cell Mol. Physiol. 283 (2002) L766-776
75. Jeyapaul J., and Jaiswal A.K. Nrf2 and c-Jun regulation of antioxidant response element (ARE)-mediated expression and induction of gamma-glutamylcysteine synthetase heavy subunit gene. Biochem. Pharmacol. 59 (2000) 1433-1439
76. Jin W., Wang H., Yan W., Zhu L., Hu Z., Ding Y., and Tang K. Role of Nrf2 in protection against traumatic brain injury in mice. J. Neurotrauma 26 (2009) 131-139
77. Jobe A.H., and Bancalari E. Bronchopulmonary dysplasia. Am. J. Respir. Crit. Care Med. 163 (2001) 1723-1729
78. Johnston C.J., Stripp B.R., Piedbeouf B., Wright T.W., Mango G.W., Reed C.K., and Finkelstein J.N. Inflammatory and epithelial responses in mouse strains that differ in sensitivity to hyperoxic injury. Exp. Lungs Res. 24 (1998) 189-202
79. Kang G.H., Lee S., Kim J.S., and Jung H.Y. Profile of aberrant CpG island methylation along multistep gastric carcinogenesis. Lab. Invest. 83 (2003) 519-526
80. Kang K.W., Lee S.J., Park J.W., and Kim S.G. Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress. Mol. Pharmacol. 62 (2002) 1001-1010
81. Kang M.I., Kobayashi A., Wakabayashi N., Kim S.G., and Yamamoto M. Scaffolding of Keap1 to the actin cytoskeleton controls the function of Nrf2 as key regulator of cytoprotective phase 2 genes. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 2046-2051
82. Katoh Y., Iida K., Kang M.I., Kobayashi A., Mizukami M., Tong K.I., McMahon M., Hayes J.D., Itoh K., and Yamamoto M. Evolutionary conserved N-terminal domain of Nrf2 is essential for the Keap1-mediated degradation of the protein by proteasome. Arch. Biochem. Biophys. 433 (2005) 342-350
83. Katsuoka F., Motohashi H., Engel J.D., and Yamamoto M. Nrf2 transcriptionally activates the mafG gene through an antioxidant response element. J. Biol. Chem. 280 (2005) 4483-4490
84. Kayanoki Y., Fujii J., Suzuki K., Kawata S., Matsuzawa Y., and Taniguchi N. Suppression of antioxidative enzyme expression by transforming growth factor-beta 1 in rat hepatocytes. J. Biol. Chem. 269 (1994) 15488-15492
85. Khor T.O., Huang M.T., Prawan A., Liu Y., Hao X., Yu S., Cheung W.K., Chan J.Y., Reddy B.S., Yang C.S., and Kong A.N. Increased susceptibility of Nrf2 knockout mice to colitis-associated colorectal cancer. Cancer Prev. Res. (Philadelphia, Pa) 1 (2008) 187-191
86. Kim H.S., Manevich Y., Feinstein S.I., Pak J.H., Ho Y.S., and Fisher A.B. Induction of 1-cys peroxiredoxin expression by oxidative stress in lung epithelial cells. Am. J. Physiol., Lung Cell Mol. Physiol. 285 (2003) L363-369
87. Kobayashi M., Itoh K., Suzuki T., Osanai H., Nishikawa K., Katoh Y., Takagi Y., and Yamamoto M. Identification of the interactive interface and phylogenic conservation of the Nrf2-Keap1 system. Genes Cells 7 (2002) 807-820
88. Kurt-Jones E.A., Popova L., Kwinn L., Haynes L.M., Jones L.P., Tripp R.A., Walsh E.E., Freeman M.W., Golenbock D.T., Anderson L.J., and Finberg R.W. Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus. Nat. Immunol. 1 (2000) 398-401
89. Kwak M.K., Itoh K., Yamamoto M., and Kensler T.W. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter. Mol. Cell. Biol. 22 (2002) 2883-2892
90. Kwak M.K., Wakabayashi N., Itoh K., Motohashi H., Yamamoto M., and Kensler T.W. Modulation of gene expression by cancer chemopreventive dithiolethiones through the Keap1-Nrf2 pathway. Identification of novel gene clusters for cell survival. J. Biol. Chem. 278 (2003) 8135-8145
91. Ledwozyw A. Protective effect of liposome-entrapped superoxide dismutase and catalase on bleomycin-induced lung injury in rats. II. Phospholipids of the lung surfactant. Acta Physiol. Hung. 78 (1991) 157-162
92. Leff J.A., Parsons P.E., Day C.E., Moore E.E., Moore F.A., Oppegard M.A., and Repine J.E. Increased serum catalase activity in septic patients with the adult respiratory distress syndrome. Am. Rev. Respir. Dis. 146 (1992) 985-989
93. Li N., Alam J., Venkatesan M.I., Eiguren-Fernandez A., Schmitz D., Di Stefano E., Slaughter N., Killeen E., Wang X., Huang A., Wang M., Miguel A.H., Cho A., Sioutas C., and Nel A.E. Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells: protecting against the proinflammatory and oxidizing effects of diesel exhaust chemicals. J. Immunol. 173 (2004) 3467-3481
94. Li Y.J., Takizawa H., Azuma A., Kohyama T., Yamauchi Y., Takahashi S., Yamamoto M., Kawada T., Kudoh S., and Sugawara I. Disruption of Nrf2 enhances susceptibility to airway inflammatory responses induced by low-dose diesel exhaust particles in mice. Clin. Immunol. 128 (2008) 366-373
95. Lin P., Hsueh Y.M., Ko J.L., Liang Y.F., Tsai K.J., and Chen C.Y. Analysis of NQO1, GSTP1, and MnSOD genetic polymorphisms on lung cancer risk in Taiwan. Lung Cancer 40 (2003) 123-129
96. Liu R.M., Liu Y., Forman H.J., Olman M., and Tarpey M.M. Glutathione regulates transforming growth factor-beta-stimulated collagen production in fibroblasts. Am. J. Physiol., Lung Cell Mol. Physiol. 286 (2004) L121-128
97. Liu T., Castro S., Brasier A.R., Jamaluddin M., Garofalo R.P., and Casola A. Reactive oxygen species mediate virus-induced STAT activation: role of tyrosine phosphatases. J. Biol. Chem. 279 (2004) 2461-2469
98. Liu W., Nakamura H., Shioji K., Tanito M., Oka S., Ahsan M.K., Son A., Ishii Y., Kishimoto C., and Yodoi J. Thioredoxin-1 ameliorates myosin-induced autoimmune myocarditis by suppressing chemokine expressions and leukocyte chemotaxis in mice. Circulation 110 (2004) 1276-1283
99. London S.J., Yuan J.M., Chung F.L., Gao Y.T., Coetzee G.A., Ross R.K., and Yu M.C. Isothiocyanates, glutathione S-transferase M1 and T1 polymorphisms, and lung-cancer risk: a prospective study of men in Shanghai, China. Lancet 356 (2000) 724-729
100. Machtay M., Scherpereel A., Santiago J., Lee J., McDonough J., Kinniry P., Arguiri E., Shuvaev V.V., Sun J., Cengel K., Solomides C.C., and Christofidou-Solomidou M. Systemic polyethylene glycol-modified (PEGylated) superoxide dismutase and catalase mixture attenuates radiation pulmonary fibrosis in the C57/bl6 mouse. Radiother. Oncol. 81 (2006) 196-205
101. Malhotra D., Thimmulappa R., Navas-Acien A., Sandford A., Elliott M., Singh A., Chen L., Zhuang X., Hogg J., Pare P., Tuder R.M., and Biswal S. Decline in NRF2-regulated antioxidants in chronic obstructive pulmonary disease lungs due to loss of its positive regulator, DJ-1. Am. J. Respir. Crit. Care Med. 178 (2008) 592-604
102. Mapp C.E., Fryer A.A., De Marzo N., Pozzato V., Padoan M., Boschetto P., Strange R.C., Hemmingsen A., and Spiteri M.A. Glutathione S-transferase GSTP1 is a susceptibility gene for occupational asthma induced by isocyanates. J. Allergy Clin. Immunol. 109 (2002) 867-872
103. Markart P., Luboeinski T., Korfei M., Schmidt R., Wygrecka M., Mahavadi P., Mayer K., Wilhelm J., Seeger W., Guenther A., and Ruppert C. Alveolar oxidative stress is associated with elevated levels of nonenzymatic low-molecular-weight antioxidants in patients with different forms of chronic fibrosing interstitial lung diseases. Antioxid. Redox Signal. 11 (2009) 227-240
104. Marzec J.M., Christie J.D., Reddy S.P., Jedlicka A.E., Vuong H., Lanken P.N., Aplenc R., Yamamoto T., Yamamoto M., Cho H.Y., and Kleeberger S.R. Functional polymorphisms in the transcription factor NRF2 in humans increase the risk of acute lung injury. Faseb J. 21 (2007) 2237-2246
105. Mata M., Ruiz A., Cerda M., Martinez-Losa M., Cortijo J., Santangelo F., Serrano-Mollar A., Llombart-Bosch A., and Morcillo E.J. Oral N-acetylcysteine reduces bleomycin-induced lung damage and mucin Muc5ac expression in rats. Eur. Respir. J. 22 (2003) 900-905
106. Matthay M.A., Zimmerman G.A., Esmon C., Bhattacharya J., Coller B., Doerschuk C.M., Floros J., Gimbrone Jr. M.A., Hoffman E., Hubmayr R.D., Leppert M., Matalon S., Munford R., Parsons P., Slutsky A.S., Tracey K.J., Ward P., Gail D.B., and Harabin A.L. Future research directions in acute lung injury: summary of a National Heart, Lung, and Blood Institute working group. Am. J. Respir. Crit. Care Med. 167 (2003) 1027-1035
107. Matthews B.D., and Noviski N. Management of oxygenation in pediatric acute hypoxemic respiratory failure. Pediatr. Pulmonol. 32 (2001) 459-470
108. Matthias C., Bockmuhl U., Jahnke V., Jones P.W., Hayes J.D., Alldersea J., Gilford J., Bailey L., Bath J., Worrall S.F., Hand P., Fryer A.A., and Strange R.C. Polymorphism in cytochrome P450 CYP2D6, CYP1A1, CYP2E1 and glutathione S-transferase, GSTM1, GSTM3, GSTT1 and susceptibility to tobacco-related cancers: studies in upper aerodigestive tract cancers. Pharmacogenetics 8 (1998) 91-100
109. McClellan R.O. Health effects of exposure to diesel exhaust particles. Annu. Rev. Pharmacol. Toxicol. 27 (1987) 279-300
110. McMahon M., Itoh K., Yamamoto M., and Hayes J.D. . Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J. Biol. Chem. 278 (2003) 21592-21600
111. McMahon M., Thomas N., Itoh K., Yamamoto M., and Hayes J.D. Dimerization of substrate adaptors can facilitate cullin-mediated ubiquitylation of proteins by a "tethering" mechanism: a two-site interaction model for the Nrf2-Keap1 complex. J. Biol. Chem. 281 (2006) 24756-24768
112. Meulener M.C., Xu K., Thomson L., Ischiropoulos H., and Bonini N.M. . Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 12517-12522
113. Meyer A., Buhl R., Kampf S., and Magnussen H. Intravenous N-acetylcysteine and lung glutathione of patients with pulmonary fibrosis and normals. Am. J. Respir. Crit. Care Med. 152 (1995) 1055-1060
114. Mochizuki M., Ishii Y., Itoh K., Iizuka T., Morishima Y., Kimura T., Kiwamoto T., Matsuno Y., Hegab A.E., Nomura A., Sakamoto T., Uchida K., Yamamoto M., and Sekizawa K. Role of 15-deoxy delta(12,14) prostaglandin J2 and Nrf2 pathways in protection against acute lung injury. Am. J. Respir. Crit. Care Med. 171 (2005) 1260-1266
115. Moore M.L., and Peebles Jr. R.S. Respiratory syncytial virus disease mechanisms implicated by human, animal model, and in vitro data facilitate vaccine strategies and new therapeutics. Pharmacol. Ther. 112 (2006) 405-424
116. Moss M., Bucher B., Moore F.A., Moore E.E., and Parsons P.E. The role of chronic alcohol abuse in the development of acute respiratory distress syndrome in adults. Jama 275 (1996) 50-54
117. Nguyen T., Huang H.C., and Pickett C.B. Transcriptional regulation of the antioxidant response element. Activation by Nrf2 and repression by MafK. J. Biol. Chem. 275 (2000) 15466-15473
118. Northway Jr. W.H., Rosan R.C., and Porter D.Y. Pulmonary disease following respirator therapy of hyaline-membrane disease. Bronchopulmonary dysplasia. N. Engl. J. Med. 276 (1967) 357-368
119. Ockenga J., Vogel A., Teich N., Keim V., Manns M.P., and Strassburg C.P. UDP glucuronosyltransferase (UGT1A7) gene polymorphisms increase the risk of chronic pancreatitis and pancreatic cancer. Gastroenterology 124 (2003) 1802-1808
120. Ohta T., Iijima K., Miyamoto M., Nakahara I., Tanaka H., Ohtsuji M., Suzuki T., Kobayashi A., Yokota J., Sakiyama T., Shibata T., Yamamoto M., and Hirohashi S. Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res. 68 (2008) 1303-1309
121. Otterbein L.E., Kolls J.K., Mantell L.L., Cook J.L., Alam J., and Choi A.M. Exogenous administration of heme oxygenase-1 by gene transfer provides protection against hyperoxia-induced lung injury. J. Clin. Invest. 103 (1999) 1047-1054
122. Oue N., Sentani K., Yokozaki H., Kitadai Y., Ito R., and Yasui W. Promoter methylation status of the DNA repair genes hMLH1 and MGMT in gastric carcinoma and metaplastic mucosa. Pathobiology 69 (2001) 143-149
123. Padmanabhan B., Tong K.I., Ohta T., Nakamura Y., Scharlock M., Ohtsuji M., Kang M.I., Kobayashi A., Yokoyama S., and Yamamoto M. Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol. Cell 21 (2006) 689-700
124. Papaiahgari S., Kleeberger S.R., Cho H.Y., Kalvakolanu D.V., and Reddy S.P. NADPH oxidase and ERK signaling regulates hyperoxia-induced Nrf2-ARE transcriptional response in pulmonary epithelial cells. J. Biol. Chem. 279 (2004) 42302-42312
125. Papaiahgari S., Yerrapureddy A., Reddy S.R., Reddy N.M., Dodd-O J.M., Crow M.T., Grigoryev D.N., Barnes K., Tuder R.M., Yamamoto M., Kensler T.W., Biswal S., Mitzner W., Hassoun P.M., and Reddy S.P. Genetic and pharmacologic evidence links oxidative stress to ventilator-induced lung injury in mice. Am. J. Respir. Crit. Care Med. 176 (2007) 1222-1235
126. Pardo A., Ruiz V., Arreola J.L., Ramirez R., Cisneros-Lira J., Gaxiola M., Barrios R., Kala S.V., Lieberman M.W., and Selman M. Bleomycin-induced pulmonary fibrosis is attenuated in gamma-glutamyl transpeptidase-deficient mice. Am. J. Respir. Crit. Care Med. 167 (2003) 925-932
127. Powers K.A., Szaszi K., Khadaroo R.G., Tawadros P.S., Marshall J.C., Kapus A., and Rotstein O.D. Oxidative stress generated by hemorrhagic shock recruits Toll-like receptor 4 to the plasma membrane in macrophages. J. Exp. Med. 203 (2006) 1951-1961
128. Rahman I. Inflammation and the regulation of glutathione level in lung epithelial cells. Antioxid. Redox. Signal. 1 (1999) 425-447
129. Rahman I., Bel A., Mulier B., Lawson M.F., Harrison D.J., Macnee W., and Smith C.A. Transcriptional regulation of gamma-glutamylcysteine synthetase-heavy subunit by oxidants in human alveolar epithelial cells. Biochem. Biophys. Res. Commun. 229 (1996) 832-837
130. Rahman I., Biswas S.K., and Kirkham P.A. Regulation of inflammation and redox signaling by dietary polyphenols. Biochem. Pharmacol. 72 (2006) 1439-1452
131. Ramos-Gomez M., Dolan P.M., Itoh K., Yamamoto M., and Kensler T.W. Interactive effects of nrf2 genotype and oltipraz on benzo[a]pyrene-DNA adducts and tumor yield in mice. Carcinogenesis 24 (2003) 461-467
132. Ramos-Gomez M., Kwak M.K., Dolan P.M., Itoh K., Yamamoto M., Talalay P., and 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. 98 (2001) 3410-3415
133. Rangasamy T., Cho C.Y., Thimmulappa R.K., Zhen L., Srisuma S.S., Kensler T.W., Yamamoto M., Petrache I., Tuder R.M., and Biswal S. Genetic ablation of Nrf2 enhances susceptibility to cigarette smoke-induced emphysema in mice. J. Clin. Invest. 114 (2004) 1248-1259
134. Rangasamy T., Guo J., Mitzner W.A., Roman J., Singh A., Fryer A.D., Yamamoto M., Kensler T.W., Tuder R.M., Georas S.N., and Biswal S. Disruption of Nrf2 enhances susceptibility to severe airway inflammation and asthma in mice. J. Exp. Med. 202 (2005) 47-59
135. Reddy N.M., Kleeberger S.R., Yamamoto M., Kensler T.W., Scollick C., Biswal S., and Reddy S.P. Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection. Physiol. Genomics. 32 (2007) 74-81
136. Repine J.E. Scientific perspectives on adult respiratory distress syndrome. Lancet 339 (1992) 466-469
137. Rushmore T.H., Morton M.R., and 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. 266 (1991) 11632-11639
138. Sadowska A.M., Manuel Y.K.B., and De Backer W.A. Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: discordant in vitro and in vivo dose-effects: a review. Pulm. Pharmacol. Ther. 20 (2007) 9-22
139. Saugstad O.D. Bronchopulmonary dysplasia-oxidative stress and antioxidants. Semin. Neonatol. 8 (2003) 39-49
140. Shibata T., Ohta T., Tong K.I., Kokubu A., Odogawa R., Tsuta K., Asamura H., Yamamoto M., and Hirohashi S. Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 13568-13573
141. Shih A.Y., Johnson D.A., Wong G., Kraft A.D., Jiang L., Erb H., Johnson J.A., and Murphy T.H. Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J. Neurosci. 23 (2003) 3394-3406
142. Siegel D., and Ross D. Immunodetection of NAD(P)H:quinone oxidoreductase 1 (NQO1) in human tissues. Free Radic. Biol. Med. 29 (2000) 246-253
143. Singh A., Boldin-Adamsky S., Thimmulappa R.K., Rath S.K., Ashush H., Coulter J., Blackford A., Goodman S.N., Bunz F., Watson W.H., Gabrielson E., Feinstein E., and Biswal S. RNAi-mediated silencing of nuclear factor erythroid-2-related factor 2 gene expression in non-small cell lung cancer inhibits tumor growth and increases efficacy of chemotherapy. Cancer Res. 68 (2008) 7975-7984
144. Singh A., Ling G., Suhasini A.N., Zhang P., Yamamoto M., Navas-Acien A., Cosgrove G., Tuder R.M., Kensler T.W., Watson W.H., and Biswal S. Nrf2-dependent sulfiredoxin-1 expression protects against cigarette smoke-induced oxidative stress in lungs. Free Radic. Biol. Med. 46 (2009) 376-386
145. Singh A., Misra V., Thimmulappa R.K., Lee H., Ames S., Hoque M.O., Herman J.G., Baylin S.B., Sidransky D., Gabrielson E., Brock M.V., and Biswal S. Dysfunctional KEAP1-NRF2 interaction in non-small-cell lung cancer. PLoS Med. 3 (2006) e420
146. Spiteri M.A., Bianco A., Strange R.C., and Fryer A.A. Polymorphisms at the glutathione S-transferase, GSTP1 locus: a novel mechanism for susceptibility and development of atopic airway inflammation. Allergy 55 Suppl. 61 (2000) 15-20
147. Sriram N., Kalayarasan S., and Sudhandiran G. Epigallocatechin-3-gallate augments antioxidant activities and inhibits inflammation during bleomycin-induced experimental pulmonary fibrosis through Nrf2-Keap1 signaling. Pulm. Pharmacol. Ther. 22 (2008) 221-236
148. Stenzel J.D., Welty S.E., Benzick A.E., Smith E.O., Smith C.V., and Hansen T.N. Hyperoxic lung injury in Fischer-344 and Sprague-Dawley rats in vivo. Free Radic. Biol. Med. 14 (1993) 531-539
149. Suzuki M., Betsuyaku T., Ito Y., Nagai K., Nasuhara Y., Kaga K., Kondo S., and Nishimura M. Down-regulated NF-E2-related factor 2 in pulmonary macrophages of aged smokers and patients with chronic obstructive pulmonary disease. Am. J. Respir. Cell Mol. Biol. 39 (2008) 673-682
150. Talalay P., and Fahey J.W. Phytochemicals from cruciferous plants protect against cancer by modulating carcinogen metabolism. J. Nutr. 131 (2001) 3027S-3033S
151. Tan X.L., and Spivack S.D. Dietary chemoprevention strategies for induction of phase II xenobiotic-metabolizing enzymes in lung carcinogenesis: a review. Lung Cancer 65 (2009) 129-137
152. Taylor J.L., Carraway M.S., and Piantadosi C.A. Lung-specific induction of heme oxygenase-1 and hyperoxic lung injury. Am. J. Physiol. 274 (1998) L582-590
153. Taylor R.C., Acquaah-Mensah G., Singhal M., Malhotra D., and Biswal S. Network inference algorithms elucidate Nrf2 regulation of mouse lung oxidative stress. PLoS Comput. Biol. 4 (2008) e1000166
154. Terui K., Takahashi Y., Kitazawa J., Toki T., Yokoyama M., and Ito E. Expression of transcription factors during megakaryocytic differentiation of CD34+ cells from human cord blood induced by thrombopoietin. Tohoku J. Exp. Med. 192 (2000) 259-273
155. Thannickal V.J., and Fanburg B.L. Reactive oxygen species in cell signaling. Am. J. Physiol., Lung Cell Mol. Physiol. 279 (2000) L1005-1028
156. Thimmulappa R.K., Fuchs R.J., Malhotra D., Scollick C., Traore K., Bream J.H., Trush M.A., Liby K.T., Sporn M.B., Kensler T.W., and Biswal S. Preclinical evaluation of targeting the Nrf2 pathway by triterpenoids (CDDO-Im and CDDO-Me) for protection from LPS-induced inflammatory response and reactive oxygen species in human peripheral blood mononuclear cells and neutrophils. Antioxid. Redox Signal. 9 (2007) 1963-1970
157. Thimmulappa R.K., Lee H., Rangasamy T., Reddy S.P., Yamamoto M., Kensler T.W., and Biswal S. Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis. J. Clin. Invest. 116 (2006) 984-995
158. Thimmulappa R.K., Scollick C., Traore K., Yates M., Trush M.A., Liby K.T., Sporn M.B., Yamamoto M., Kensler T.W., and Biswal S. Nrf2-dependent protection from LPS induced inflammatory response and mortality by CDDO-Imidazolide. Biochem. Biophys. Res. Commun. 351 (2006) 883-889
159. Thompson K., Menzies S., Muckenthaler M., Torti F.M., Wood T., Torti S.V., Hentze M.W., Beard J., and Connor J. Mouse brains deficient in H-ferritin have normal iron concentration but a protein profile of iron deficiency and increased evidence of oxidative stress. J. Neurosci. Res. 71 (2003) 46-63
160. Tian L., White J.E., Lin H.Y., Haran V.S., Sacco J., Chikkappa G., Davis F.B., Davis P.J., and Tsan M.F. Induction of Mn SOD in human monocytes without inflammatory cytokine production by a mutant endotoxin. Am. J. Physiol. 275 (1998) C740-747
161. Tirumalai R., Rajesh Kumar T., Mai K.H., and Biswal S. Acrolein causes transcriptional induction of phase II genes by activation of Nrf2 in human lung type II epithelial (A549) cells. Toxicol. Lett. 132 (2002) 27-36
162. Tripp R.A., Jones L.P., Haynes L.M., Zheng H., Murphy P.M., and Anderson L.J. CX3C chemokine mimicry by respiratory syncytial virus G glycoprotein. Nat. Immunol. 2 (2001) 732-738
163. Uings I.J., and Farrow S.N. Cell receptors and cell signalling. Mol. Pathol. 53 (2000) 295-299
164. Vallyathan V., Shi X., and Castranova V. Reactive oxygen species: their relation to pneumoconiosis and carcinogenesis. Environ. Health Perspect. 106 Suppl. 5 (1998) 1151-1155
165. van Schaik S.M., Obot N., Enhorning G., Hintz K., Gross K., Hancock G.E., Stack A.M., and Welliver R.C. Role of interferon gamma in the pathogenesis of primary respiratory syncytial virus infection in BALB/c mice. J. Med. Virol. 62 (2000) 257-266
166. Venugopal R., and 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. 93 (1996) 14960-14965
167. Wakabayashi N., Itoh K., Wakabayashi J., Motohashi H., Noda S., Takahashi S., Imakado S., Kotsuji T., Otsuka F., Roop D.R., Harada T., Engel J.D., and Yamamoto M. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat. Genet. 35 (2003) 238-245
168. Walter N., Collard H.R., and King Jr. T.E. Current perspectives on the treatment of idiopathic pulmonary fibrosis. Proc. Am. Thorac. Soc. 3 (2006) 330-338
169. Wang R., An J., Ji F., Jiao H., Sun H., and Zhou D. Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem. Biophys. Res. Commun. 373 (2008) 151-154
170. Wang X., Tomso D.J., Chorley B.N., Cho H.Y., Cheung V.G., Kleeberger S.R., and Bell D.A. Identification of polymorphic antioxidant response elements in the human genome. Hum. Mol. Genet. 16 (2007) 1188-1200
171. Wang Y., Feinstein S.I., Manevich Y., Ho Y.S., and Fisher A.B. Lung injury and mortality with hyperoxia are increased in peroxiredoxin 6 gene-targeted mice. Free Radic. Biol. Med. 37 (2004) 1736-1743
172. Wang Y., Manevich Y., Feinstein S.I., and Fisher A.B. Adenovirus-mediated transfer of the 1-cys peroxiredoxin gene to mouse lung protects against hyperoxic injury. Am. J. Physiol., Lung Cell Mol. Physiol. 286 (2004) L1188-1193
173. Ware L.B., Camerer E., Welty-Wolf K., Schultz M.J., and Matthay M.A. Bench to bedside: targeting coagulation and fibrinolysis in acute lung injury. Am. J. Physiol., Lung Cell Mol. Physiol. 291 (2006) L307-311
174. Ware L.B., and Matthay M.A. The acute respiratory distress syndrome. N. Engl. J. Med. 342 (2000) 1334-1349
175. Wasserman W.W., and Fahl W.E. Functional antioxidant responsive elements. Proc. Natl. Acad. Sci. U. S. A. 94 (1997) 5361-5366
176. Whitney P.L., and Frank L. Does lung NAD(P)H:quinone reductase (DT-diaphorase) play an antioxidant enzyme role in protection from hyperoxia?. Biochim. Biophys. Acta 1156 (1993) 275-282
177. Williams M.A., Rangasamy T., Bauer S.M., Killedar S., Karp M., Kensler T.W., Yamamoto M., Breysse P., Biswal S., and Georas S.N. Disruption of the transcription factor Nrf2 promotes pro-oxidative dendritic cells that stimulate Th2-like immunoresponsiveness upon activation by ambient particulate matter. J. Immunol. 181 (2008) 4545-4559
178. Yamamoto M., Yang G., Hong C., Liu J., Holle E., Yu X., Wagner T., Vatner S.F., and Sadoshima J. Inhibition of endogenous thioredoxin in the heart increases oxidative stress and cardiac hypertrophy. J. Clin. Invest. 112 (2003) 1395-1406
179. Yamamoto T., Yoh K., Kobayashi A., Ishii Y., Kure S., Koyama A., Sakamoto T., Sekizawa K., Motohashi H., and Yamamoto M. Identification of polymorphisms in the promoter region of the human NRF2 gene. Biochem. Biophys. Res. Commun. 321 (2004) 72-79
180. Zhang D.D., and Hannink M. Distinct cysteine residues in Keap1 are required for Keap1-dependent ubiquitination of Nrf2 and for stabilization of Nrf2 by chemopreventive agents and oxidative stress. Mol. Cell. Biol. 23 (2003) 8137-8151
181. Zhang Y., Kensler T.W., Cho C.G., Posner G.H., and Talalay P. Anticarcinogenic activities of sulforaphane and structurally related synthetic norbornyl isothiocyanates. Proc. Natl. Acad. Sci. U. S. A. 91 (1994) 3147-3150
182. Zhu M., and Fahl W.E. Functional characterization of transcription regulators that interact with the electrophile response element. Biochem. Biophys. Res. Commun. 289 (2001) 212-219
183. Zipper L.M., and Mulcahy R.T. The Keap1 BTB/POZ dimerization function is required to sequester Nrf2 in cytoplasm. J. Biol. Chem. 277 (2002) 36544-36552