| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 275, Issue 21, 16023-16029, May 26, 2000
From the Institute of Basic Medical Sciences and Center for Tsukuba
Advanced Research Alliance, University of Tsukuba, 1-1-1 Tennoudai,
Tsukuba 305-8577, Japan
Electrophiles and reactive oxygen species have
been implicated in the pathogenesis of many diseases. Transcription
factor Nrf2 was recently identified as a general regulator of
one defense mechanism against such havoc. Nrf2 regulates the
inducible expression of a group of detoxication enzymes, such as
glutathione S-transferase and NAD(P)H:quinone
oxidoreductase, via antioxidant response elements. Using peritoneal
macrophages from Nrf2-deficient mice, we show here that
Nrf2 also controls the expression of a group of electrophile- and oxidative stress-inducible proteins and activities, which includes
heme oxygenase-1, A170, peroxiredoxin MSP23, and cystine membrane
transport (system xc
Transcription Factor Nrf2 Coordinately Regulates a Group
of Oxidative Stress-inducible Genes in Macrophages*
,§,
) activity. The
response to electrophilic and reactive oxygen species-producing agents
was profoundly impaired in Nrf2-deficient cells. The lack of
induction of system xc activity
resulted in the minimum level of intracellular glutathione, and
Nrf2-deficient cells were more sensitive to toxic electrophiles. Several stress agents induced the DNA binding activity of Nrf2 in the nucleus without increasing its mRNA level. Thus Nrf2
regulates a wide-ranging metabolic response to oxidative stress.
*
This work was supported in part by grants-in-aid from the
Ministry of Education, Science, Sports and Culture, the Japanese Society for Promotion of Sciences (JSPS), and CREST.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
These two authors contributed equally to this work.
§
Research Fellow of the JSPS.
¶
To whom correspondence should be addressed: Center for TARA,
University of Tsukuba, 1-1-1 Tennoudai, Tsukuba 305-8577, Japan. Tel.:
81-298-53-6158; Fax: 81-298-53-7318; E-mail: masi@tara. tsukuba.ac.jp.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  M. Suzuki, T. Betsuyaku, Y. Ito, K. Nagai, Y. Nasuhara, K. Kaga, S. Kondo, and M. Nishimura 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., December 1, 2008; 39(6): 673 - 682. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Nishimura, Y. Dewa, T. Okamura, M. Jin, Y. Saegusa, M. Kawai, T. Umemura, M. Shibutani, and K. Mitsumori Role of Nrf2 and Oxidative stress on Fenofibrate-Induced Hepatocarcinogenesis in Rats Toxicol. Sci., December 1, 2008; 106(2): 339 - 349. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Rushworth, D. J. MacEwan, and M. A. O'Connell Lipopolysaccharide-Induced Expression of NAD(P)H:Quinone Oxidoreductase 1 and Heme Oxygenase-1 Protects against Excessive Inflammatory Responses in Human Monocytes J. Immunol., November 15, 2008; 181(10): 6730 - 6737. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Okada, J. Shoda, K. Taguchi, J. M. Maher, K. Ishizaki, Y. Inoue, M. Ohtsuki, N. Goto, K. Takeda, H. Utsunomiya, et al. Ursodeoxycholic acid stimulates Nrf2-mediated hepatocellular transport, detoxification, and antioxidative stress systems in mice Am J Physiol Gastrointest Liver Physiol, October 1, 2008; 295(4): G735 - G747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ueda, T. Ueyama, K.-i. Yoshida, H. Kimura, T. Ito, Y. Shimizu, M. Oka, Y. Tsuruo, and M. Ichinose Adaptive HNE-Nrf2-HO-1 pathway against oxidative stress is associated with acute gastric mucosal lesions Am J Physiol Gastrointest Liver Physiol, September 1, 2008; 295(3): G460 - G469. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Mito, R. Ozono, T. Oshima, Y. Yano, Y. Watari, Y. Yamamoto, A. Brydun, K. Igarashi, and M. Yoshizumi Myocardial Protection Against Pressure Overload in Mice Lacking Bach1, a Transcriptional Repressor of Heme Oxygenase-1 Hypertension, June 1, 2008; 51(6): 1570 - 1577. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bukowska, L. Schild, G. Keilhoff, D. Hirte, M. Neumann, A. Gardemann, K. H. Neumann, F.-W. Rohl, C. Huth, A. Goette, et al. Mitochondrial Dysfunction and Redox Signaling in Atrial Tachyarrhythmia Experimental Biology and Medicine, May 1, 2008; 233(5): 558 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Dooley, S. Y. Low, A. Holmes, A. G. Kidane, D. J. Abraham, C. M. Black, and K. R. Bruckdorfer Nitric oxide synthase expression and activity in the tight-skin mouse model of fibrosis Rheumatology, March 1, 2008; 47(3): 272 - 280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sarioglu, S. Brandner, M. Haberger, C. Jacobsen, J. Lichtmannegger, M. Wormke, and U. Andrae Analysis of 2,3,7,8-Tetrachlorodibenzo-p-dioxin-induced Proteome Changes in 5L Rat Hepatoma Cells Reveals Novel Targets of Dioxin Action Including the Mitochondrial Apoptosis Regulator VDAC2 Mol. Cell. Proteomics, February 1, 2008; 7(2): 394 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Suzuki, V. P. Kelly, H. Motohashi, O. Nakajima, S. Takahashi, S. Nishimura, and M. Yamamoto Deletion of the Selenocysteine tRNA Gene in Macrophages and Liver Results in Compensatory Gene Induction of Cytoprotective Enzymes by Nrf2 J. Biol. Chem., January 25, 2008; 283(4): 2021 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Diet, K. Abbas, C. Bouton, B. Guillon, F. Tomasello, S. Fourquet, M. B. Toledano, and J.-C. Drapier Regulation of Peroxiredoxins by Nitric Oxide in Immunostimulated Macrophages J. Biol. Chem., December 14, 2007; 282(50): 36199 - 36205. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. T. Jacobs and L. J. Marnett Heat Shock Factor 1 Attenuates 4-Hydroxynonenal-mediated Apoptosis: CRITICAL ROLE FOR HEAT SHOCK PROTEIN 70 INDUCTION AND STABILIZATION OF Bcl-XL J. Biol. Chem., November 16, 2007; 282(46): 33412 - 33420. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rokushima, K. Omi, K. Imura, A. Araki, N. Furukawa, F. Itoh, M. Miyazaki, J. Yamamoto, M. Rokushima, M. Okada, et al. Toxicogenomics of Drug-Induced Hemolytic Anemia by Analyzing Gene Expression Profiles in the Spleen Toxicol. Sci., November 1, 2007; 100(1): 290 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sumimoto, S. Kamakura, and T. Ito Structure and Function of the PB1 Domain, a Protein Interaction Module Conserved in Animals, Fungi, Amoebas, and Plants Sci. Signal., August 28, 2007; 2007(401): re6 - re6. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. E. Mann, D. J. Rowlands, F. Y.L. Li, P. de Winter, and R. C.M. Siow Activation of endothelial nitric oxide synthase by dietary isoflavones: Role of NO in Nrf2-mediated antioxidant gene expression Cardiovasc Res, July 15, 2007; 75(2): 261 - 274. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Villacorta, J. Zhang, M. T. Garcia-Barrio, X.-l. Chen, B. A. Freeman, Y. E. Chen, and T. Cui Nitro-linoleic acid inhibits vascular smooth muscle cell proliferation via the Keap1/Nrf2 signaling pathway Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H770 - H776. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Aoki, A. H. Hashimoto, K. Amanuma, M. Matsumoto, K. Hiyoshi, H. Takano, K.-i. Masumura, K. Itoh, T. Nohmi, and M. Yamamoto Enhanced Spontaneous and Benzo(a)pyrene-Induced Mutations in the Lung of Nrf2-Deficient gpt Delta Mice Cancer Res., June 15, 2007; 67(12): 5643 - 5648. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Aleksunes and J. E. Manautou Emerging Role of Nrf2 in Protecting Against Hepatic and Gastrointestinal Disease Toxicol Pathol, June 1, 2007; 35(4): 459 - 473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Haschemi, O. Wagner, R. Marculescu, B. Wegiel, S. C. Robson, N. Gagliani, D. Gallo, J.-F. Chen, F. H. Bach, and L. E. Otterbein Cross-Regulation of Carbon Monoxide and the Adenosine A2a Receptor in Macrophages J. Immunol., May 1, 2007; 178(9): 5921 - 5929. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Okada, J. Shoda, M. Kano, S. Suzuki, N. Ohtake, M. Yamamoto, H. Takahashi, H. Utsunomiya, K. Oda, K. Sato, et al. Inchinkoto, a herbal medicine, and its ingredients dually exert Mrp2/MRP2-mediated choleresis and Nrf2-mediated antioxidative action in rat livers Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1450 - G1463. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M.-F. Yueh and R. H. Tukey Nrf2-Keap1 Signaling Pathway Regulates Human UGT1A1 Expression in Vitro and in Transgenic UGT1 Mice J. Biol. Chem., March 23, 2007; 282(12): 8749 - 8758. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Liu, J. T. Kern, J. R. Walker, J. A. Johnson, P. G. Schultz, and H. Luesch A genomic screen for activators of the antioxidant response element PNAS, March 20, 2007; 104(12): 5205 - 5210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Li, W. Chen, R. Yanes, S. Lee, and J. A. Berliner OKL38 is an oxidative stress response gene stimulated by oxidized phospholipids J. Lipid Res., March 1, 2007; 48(3): 709 - 715. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-J. Kim, J.-Y. Ahn, P. Liang, C. Ip, Y. Zhang, and Y.-M. Park Human prx1 Gene Is a Target of Nrf2 and Is Up-regulated by Hypoxia/Reoxygenation: Implication to Tumor Biology Cancer Res., January 15, 2007; 67(2): 546 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Faraonio, P. Vergara, D. Di Marzo, M. G. Pierantoni, M. Napolitano, T. Russo, and F. Cimino p53 Suppresses the Nrf2-dependent Transcription of Antioxidant Response Genes J. Biol. Chem., December 29, 2006; 281(52): 39776 - 39784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Aburaya, K.-I. Tanaka, T. Hoshino, S. Tsutsumi, K. Suzuki, M. Makise, R. Akagi, and T. Mizushima Heme Oxygenase-1 Protects Gastric Mucosal Cells against Non-steroidal Anti-inflammatory Drugs J. Biol. Chem., November 3, 2006; 281(44): 33422 - 33432. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, T. Ohta, A. Maruyama, T. Hosoya, K. Nishikawa, J. M. Maher, S. Shibahara, K. Itoh, and M. Yamamoto BRG1 Interacts with Nrf2 To Selectively Mediate HO-1 Induction in Response to Oxidative Stress Mol. Cell. Biol., November 1, 2006; 26(21): 7942 - 7952. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Hagemann, J. X. Connor, and A. Messing Alexander Disease-Associated Glial Fibrillary Acidic Protein Mutations in Mice Induce Rosenthal Fiber Formation and a White Matter Stress Response J. Neurosci., October 25, 2006; 26(43): 11162 - 11173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Andoh, A. Mizutani, T. Ohashi, S. Kojo, T. Ishii, Y. Adachi, S. Ikehara, and S. Taketani The Antioxidant Role of a Reagent, 2',7'-Dichlorodihydrofluorescin Diacetate, Detecting Reactive-Oxygen Species and Blocking the Induction of Heme Oxygenase-1 and Preventing Cytotoxicity J. Biochem., October 1, 2006; 140(4): 483 - 489. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Rodrigo, S. Trujillo, and C. Bosco Biochemical and Ultrastructural Lung Damage Induced by Rhabdomyolysis in the Rat Experimental Biology and Medicine, September 1, 2006; 231(8): 1430 - 1438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. McMahon, N. Thomas, K. Itoh, M. Yamamoto, and J. D. Hayes 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., August 25, 2006; 281(34): 24756 - 24768. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. S. Ko, S. J. Lee, J. W. Kim, J. W. Lim, and S. G. Kim DIFFERENTIAL EFFECTS OF THE OXIDIZED METABOLITES OF OLTIPRAZ ON THE ACTIVATION OF CCAAT/ENHANCER BINDING PROTEIN-{beta} AND NF-E2-RELATED FACTOR-2 FOR GSTA2 GENE INDUCTION Drug Metab. Dispos., August 1, 2006; 34(8): 1353 - 1360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Yoshinari, N. Okino, T. Sato, J. Sugatani, and M. Miwa INDUCTION OF DETOXIFYING ENZYMES IN RODENT WHITE ADIPOSE TISSUE BY ARYL HYDROCARBON RECEPTOR AGONISTS AND ANTIOXIDANTS Drug Metab. Dispos., July 1, 2006; 34(7): 1081 - 1089. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Yano, R. Ozono, Y. Oishi, M. Kambe, M. Yoshizumi, T. Ishida, S. Omura, T. Oshima, and K. Igarashi Genetic ablation of the transcription repressor Bach1 leads to myocardial protection against ischemia/reperfusion in mice. Genes Cells, July 1, 2006; 11(7): 791 - 803. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Wood-Allum, S. C. Barber, J. Kirby, P. Heath, H. Holden, R. Mead, A. Higginbottom, S. Allen, T. Beaujeux, S. E. Alexson, et al. Impairment of mitochondrial anti-oxidant defence in SOD1-related motor neuron injury and amelioration by ebselen Brain, July 1, 2006; 129(7): 1693 - 1709. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hinoi, S. Fujimori, L. Wang, H. Hojo, K. Uno, and Y. Yoneda Nrf2 Negatively Regulates Osteoblast Differentiation via Interfering with Runx2-dependent Transcriptional Activation J. Biol. Chem., June 30, 2006; 281(26): 18015 - 18024. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Cauchi, W. Han, S. V. Kumar, and S. D. Spivack Haplotype-environment interactions that regulate the human glutathione s-transferase p1 promoter. Cancer Res., June 15, 2006; 66(12): 6439 - 6448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Goldring, N. Kitteringham, R. Jenkins, I. Copple, J.-F. Jeannin, and B. K. Park Plasticity in cell defence: access to and reactivity of critical protein residues and DNA response elements J. Exp. Biol., June 15, 2006; 209(12): 2337 - 2343. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. auf dem Keller, M. Huber, T. A. Beyer, A. Kumin, C. Siemes, S. Braun, P. Bugnon, V. Mitropoulos, D. A. Johnson, J. A. Johnson, et al. Nrf Transcription Factors in Keratinocytes Are Essential for Skin Tumor Prevention but Not for Wound Healing Mol. Cell. Biol., May 15, 2006; 26(10): 3773 - 3784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-L. Chen, G. Dodd, S. Thomas, X. Zhang, M. A. Wasserman, B. H. Rovin, and C. Kunsch Activation of Nrf2/ARE pathway protects endothelial cells from oxidant injury and inhibits inflammatory gene expression Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1862 - H1870. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Umemura, Y. Kuroiwa, Y. Kitamura, Y. Ishii, K. Kanki, Y. Kodama, K. Itoh, M. Yamamoto, A. Nishikawa, and M. Hirose A Crucial Role of Nrf2 in In Vivo Defense against Oxidative Damage by an Environmental Pollutant, Pentachlorophenol Toxicol. Sci., March 1, 2006; 90(1): 111 - 119. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. Blackburn, K. I. Matthaei, C. Lim, M. C. Taylor, J. Y. Cappello, J. D. Hayes, M. W. Anders, and P. G. Board Deficiency of Glutathione Transferase Zeta Causes Oxidative Stress and Activation of Antioxidant Response Pathways Mol. Pharmacol., February 1, 2006; 69(2): 650 - 657. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Maher and A. Hanneken Flavonoids Protect Retinal Ganglion Cells from Oxidative Stress-Induced Death Invest. Ophthalmol. Vis. Sci., December 1, 2005; 46(12): 4796 - 4803. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Iizuka, Y. Ishii, K. Itoh, T. Kiwamoto, T. Kimura, Y. Matsuno, Y. Morishima, A. E. Hegab, S. Homma, A. Nomura, et al. Nrf2-deficient mice are highly susceptible to cigarette smoke-induced emphysema Genes Cells, December 1, 2005; 10(12): 1113 - 1125. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Bjorkoy, T. Lamark, A. Brech, H. Outzen, M. Perander, A. Overvatn, H. Stenmark, and T. Johansen p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death J. Cell Biol., November 21, 2005; 171(4): 603 - 614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ishii, K. Itoh, Y. Morishima, T. Kimura, T. Kiwamoto, T. IIzuka, A. E. Hegab, T. Hosoya, A. Nomura, T. Sakamoto, et al. Transcription Factor Nrf2 Plays a Pivotal Role in Protection against Elastase-Induced Pulmonary Inflammation and Emphysema J. Immunol., November 15, 2005; 175(10): 6968 - 6975. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Y. Shih, P. Li, and T. H. Murphy A Small-Molecule-Inducible Nrf2-Mediated Antioxidant Response Provides Effective Prophylaxis against Cerebral Ischemia In Vivo J. Neurosci., November 2, 2005; 25(44): 10321 - 10335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Rushworth, X.-L. Chen, N. Mackman, R. M. Ogborne, and M. A. O'Connell Lipopolysaccharide-Induced Heme Oxygenase-1 Expression in Human Monocytic Cells Is Mediated via Nrf2 and Protein Kinase C J. Immunol., October 1, 2005; 175(7): 4408 - 4415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Nguyen, P. J. Sherratt, P. Nioi, C. S. Yang, and C. B. Pickett Nrf2 Controls Constitutive and Inducible Expression of ARE-driven Genes through a Dynamic Pathway Involving Nucleocytoplasmic Shuttling by Keap1 J. Biol. Chem., September 16, 2005; 280(37): 32485 - 32492. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Katsuoka, H. Motohashi, T. Ishii, H. Aburatani, J. D. Engel, and M. Yamamoto Genetic Evidence that Small Maf Proteins Are Essential for the Activation of Antioxidant Response Element-Dependent Genes Mol. Cell. Biol., September 15, 2005; 25(18): 8044 - 8051. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Morita Heme Oxygenase and Atherosclerosis Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1786 - 1795. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D. Zhang, S.-C. Lo, Z. Sun, G. M. Habib, M. W. Lieberman, and M. Hannink Ubiquitination of Keap1, a BTB-Kelch Substrate Adaptor Protein for Cul3, Targets Keap1 for Degradation by a Proteasome-independent Pathway J. Biol. Chem., August 26, 2005; 280(34): 30091 - 30099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. L. Hagemann, S. A. Gaeta, M. A. Smith, D. A. Johnson, J. A. Johnson, and A. Messing Gene expression analysis in mice with elevated glial fibrillary acidic protein and Rosenthal fibers reveals a stress response followed by glial activation and neuronal dysfunction Hum. Mol. Genet., August 15, 2005; 14(16): 2443 - 2458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hosoya, A. Maruyama, M.-I. Kang, Y. Kawatani, T. Shibata, K. Uchida, K. Itoh, and M. Yamamoto Differential Responses of the Nrf2-Keap1 System to Laminar and Oscillatory Shear Stresses in Endothelial Cells J. Biol. Chem., July 22, 2005; 280(29): 27244 - 27250. [Abstract] [Full Text] [PDF]
|
|
|
|
