This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Banning, A.
Right arrow Articles by Brigelius-Flohé, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Banning, A.
Right arrow Articles by Brigelius-Flohé, R.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, June 2005, p. 4914-4923, Vol. 25, No. 12
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.12.4914-4923.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The GI-GPx Gene Is a Target for Nrf2

Antje Banning,1 Stefanie Deubel,1 Dirk Kluth,1 Zewen Zhou,1 and Regina Brigelius-Flohé1,2*

German Institute of Human Nutrition, Potsdam-Rehbruecke, Dept. Biochemistry of Micronutrients,1 Institute of Nutritional Sciences, University of Potsdam, D-14558 Nuthetal, Germany2

Received 5 November 2004/ Returned for modification 10 December 2004/ Accepted 17 March 2005

The gastrointestinal glutathione peroxidase (GI-GPx, GPx2) is a selenoprotein that was suggested to act as barrier against hydroperoxide absorption but has also been implicated in the control of inflammation and malignant growth. In CaCo-2 cells, GI-GPx was induced by t-butyl hydroquinone (tBHQ) and sulforaphane (SFN), i.e., "antioxidants" known to activate the "antioxidant response element" (ARE) via electrophilic thiol modification of Keap1 in the Nrf2/Keap1 system. The functional significance of a putative ARE in the GI-GPx promoter was validated by transcriptional activation of reporter gene constructs upon exposure to electrophiles (tBHQ, SFN, and curcumin) or overexpression of Nrf2 and by reversal of these effects by mutation of the ARE in the promoter and by overexpressed Keap1. Binding of Nrf2 to the ARE sequence in authentic gpx2 was corroborated by chromatin immunoprecipitation. Thus, the presumed natural antioxidants sulforaphane and curcumin may exert their anti-inflammatory and anticarcinogenic effects not only by induction of phase 2 enzymes but also by the up-regulation of the selenoprotein GI-GPx.

* Corresponding author. Mailing address: German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany. Phone: 49-33200-88-353. Fax: 49-33200-88-407. E-mail: flohe{at}mail.dife.de.

Molecular and Cellular Biology, June 2005, p. 4914-4923, Vol. 25, No. 12
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.12.4914-4923.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Kansanen, E., Jyrkkanen, H.-K., Volger, O. L., Leinonen, H., Kivela, A. M., Hakkinen, S.-K., Woodcock, S. R., Schopfer, F. J., Horrevoets, A. J., Yla-Herttuala, S., Freeman, B. A., Levonen, A.-L. (2009). Nrf2-dependent and -independent Responses to Nitro-fatty Acids in Human Endothelial Cells: IDENTIFICATION OF HEAT SHOCK RESPONSE AS THE MAJOR PATHWAY ACTIVATED BY NITRO-OLEIC ACID. J. Biol. Chem. 284: 33233-33241 [Abstract] [Full Text]  
  • Piccirillo, S., Filomeni, G., Brune, B., Rotilio, G., Ciriolo, M. R. (2009). Redox Mechanisms Involved in the Selective Activation of Nrf2-mediated Resistance Versus p53-dependent Apoptosis in Adenocarcinoma Cells. J. Biol. Chem. 284: 27721-27733 [Abstract] [Full Text]  
  • Dreger, H., Westphal, K., Wilck, N., Baumann, G., Stangl, V., Stangl, K., Meiners, S. (2009). Protection of vascular cells from oxidative stress by proteasome inhibition depends on Nrf2. Cardiovasc Res 0: cvp279v2-cvp279 [Abstract] [Full Text]  
  • Dreger, H., Westphal, K., Weller, A., Baumann, G., Stangl, V., Meiners, S., Stangl, K. (2009). Nrf2-dependent upregulation of antioxidative enzymes: a novel pathway for proteasome inhibitor-mediated cardioprotection. Cardiovasc Res 83: 354-361 [Abstract] [Full Text]  
  • WIEGAND, H., WAGNER, A. E., BOESCH-SAADATMANDI, C., KRUSE, H.-P., KULLING, S., RIMBACH, G. (2009). Effect of Dietary Genistein on Phase II and Antioxidant Enzymes in Rat Liver. Cancer Genomics Proteomics 6: 85-92 [Abstract] [Full Text]  
  • Lu, J., Holmgren, A. (2009). Selenoproteins. J. Biol. Chem. 284: 723-727 [Abstract] [Full Text]  
  • Banning, A., Kipp, A., Schmitmeier, S., Lowinger, M., Florian, S., Krehl, S., Thalmann, S., Thierbach, R., Steinberg, P., Brigelius-Flohe, R. (2008). Glutathione Peroxidase 2 Inhibits Cyclooxygenase-2-Mediated Migration and Invasion of HT-29 Adenocarcinoma Cells but Supports Their Growth as Tumors in Nude Mice. Cancer Res. 68: 9746-9753 [Abstract] [Full Text]  
  • Zhu, H., Jia, Z., Zhang, L., Yamamoto, M., Misra, H. P., Trush, M. A., Li, Y. (2008). Antioxidants and Phase 2 Enzymes in Macrophages: Regulation by Nrf2 Signaling and Protection Against Oxidative and Electrophilic Stress. Exp. Biol. Med. 233: 463-474 [Abstract] [Full Text]  
  • Suzuki, T., Kelly, V. P., Motohashi, H., Nakajima, O., Takahashi, S., Nishimura, S., Yamamoto, M. (2008). Deletion of the Selenocysteine tRNA Gene in Macrophages and Liver Results in Compensatory Gene Induction of Cytoprotective Enzymes by Nrf2. J. Biol. Chem. 283: 2021-2030 [Abstract] [Full Text]  
  • Lee, O.-H., Jain, A. K., Papusha, V., Jaiswal, A. K. (2007). An Auto-regulatory Loop between Stress Sensors INrf2 and Nrf2 Controls Their Cellular Abundance. J. Biol. Chem. 282: 36412-36420 [Abstract] [Full Text]  
  • Aleksunes, L. M., Manautou, J. E. (2007). Emerging Role of Nrf2 in Protecting Against Hepatic and Gastrointestinal Disease. Toxicol Pathol 35: 459-473 [Abstract] [Full Text]  
  • Ebert, B., Seidel, A., Lampen, A. (2007). Phytochemicals Induce Breast Cancer Resistance Protein in Caco-2 Cells and Enhance the Transport of Benzo[a]pyrene-3-sulfate. Toxicol Sci 96: 227-236 [Abstract] [Full Text]  
  • Singh, A., Rangasamy, T., Thimmulappa, R. K., Lee, H., Osburn, W. O., Brigelius-Flohe, R., Kensler, T. W., Yamamoto, M., Biswal, S. (2006). Glutathione Peroxidase 2, the Major Cigarette Smoke-Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2. Am. J. Respir. Cell Mol. Bio. 35: 639-650 [Abstract] [Full Text]  
  • Gupta, R. K., Miller, K. P., Babus, J. K., Flaws, J. A. (2006). Methoxychlor Inhibits Growth and Induces Atresia of Antral Follicles through an Oxidative Stress Pathway. Toxicol Sci 93: 382-389 [Abstract] [Full Text]  
  • Rodrigo, R., Trujillo, S., Bosco, C. (2006). Biochemical and Ultrastructural Lung Damage Induced by Rhabdomyolysis in the Rat. Exp. Biol. Med. 231: 1430-1438 [Abstract] [Full Text]  
  • Yan, W., Chen, X. (2006). GPX2, a Direct Target of p63, Inhibits Oxidative Stress-induced Apoptosis in a p53-dependent Manner. J. Biol. Chem. 281: 7856-7862 [Abstract] [Full Text]  
  • Filomeni, G., Aquilano, K., Rotilio, G., Ciriolo, M. R. (2005). Glutathione-Related Systems and Modulation of Extracellular Signal-Regulated Kinases Are Involved in the Resistance of AGS Adenocarcinoma Gastric Cells to Diallyl Disulfide-Induced Apoptosis. Cancer Res. 65: 11735-11742 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»