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 Yang, H.
Right arrow Articles by Lu, S. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Yang, H.
Right arrow Articles by Lu, S. C.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, July 2005, p. 5933-5946, Vol. 25, No. 14
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.14.5933-5946.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Nrf1 and Nrf2 Regulate Rat Glutamate-Cysteine Ligase Catalytic Subunit Transcription Indirectly via NF-{kappa}B and AP-1

Heping Yang,1 Nathaniel Magilnick,1 Candy Lee,2 Denise Kalmaz,1 Xiaopeng Ou,1 Jefferson Y. Chan,2 and Shelly C. Lu1*

Division of Gastroenterology and Liver Diseases, USC Research Center for Liver Diseases, USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, Keck School of Medicine USC, Los Angeles, California 90033,1 Department of Pathology, University of California, Irvine, Irvine, California 926972

Received 20 August 2004/ Returned for modification 4 November 2004/ Accepted 12 April 2005

Glutamate-cysteine ligase catalytic subunit (GCLC) is regulated transcriptionally by Nrf1 and Nrf2. tert-Butylhydroquinone (TBH) induces human GCLC via Nrf2-mediated trans activation of the antioxidant-responsive element (ARE). Interestingly, TBH also induces rat GCLC, but the rat GCLC promoter lacks ARE. This study examined the role of Nrf1 and Nrf2 in the transcriptional regulation of rat GCLC. The baseline and TBH-mediated increase in GCLC mRNA levels and rat GCLC promoter activity were lower in Nrf1 and Nrf2 null (F1 and F2) fibroblasts than in wild-type cells. The basal protein and mRNA levels and nuclear binding activities of c-Jun, c-Fos, p50, and p65 were lower in F1 and F2 cells and exhibited a blunted response to TBH. Lower c-Jun and p65 expression also occurs in Nrf2 null livers. Levels of other AP-1 and NF-{kappa}B family members were either unaffected (i.e., JunB) or increased (i.e., Fra-1). Overexpression of Nrf1 and Nrf2 in respective cells restored the rat GCLC promoter activity and response to TBH but not if the AP-1 and NF-{kappa}B binding sites were mutated. Fra-1 overexpression lowered endogenous GCLC expression and rat GCLC promoter activity, while Fra-1 antisense had the opposite effects. In conclusion, Nrf1 and Nrf2 regulate rat GCLC promoter by modulating the expression of key AP-1 and NF-{kappa}B family members.

* Corresponding author. Mailing address: Division of Gastrointestinal and Liver Diseases, HMR Bldg., 415, Department of Medicine, Keck School of Medicine USC, 2011 Zonal Ave., Los Angeles, CA 90033. Phone: (323) 442-2441. Fax: (323) 442-3234. E-mail: shellylu{at}usc.edu.

Molecular and Cellular Biology, July 2005, p. 5933-5946, Vol. 25, No. 14
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.14.5933-5946.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Hoang, Y. D., Nakamura, B. N., Luderer, U. (2009). Follicle-Stimulating Hormone and Estradiol Interact to Stimulate Glutathione Synthesis in Rat Ovarian Follicles and Granulosa Cells. Biol. Reprod. 81: 636-646 [Abstract] [Full Text]  
  • Cortese-Krott, M. M., Suschek, C. V., Wetzel, W., Kroncke, K.-D., Kolb-Bachofen, V. (2009). Nitric oxide-mediated protection of endothelial cells from hydrogen peroxide is mediated by intracellular zinc and glutathione. Am. J. Physiol. Cell Physiol. 296: C811-C820 [Abstract] [Full Text]  
  • Ding, Y., Choi, K. J., Kim, J. H., Han, X., Piao, Y., Jeong, J.-H., Choe, W., Kang, I., Ha, J., Forman, H. J., Lee, J., Yoon, K.-S., Kim, S. S. (2008). Endogenous Hydrogen Peroxide Regulates Glutathione Redox via Nuclear Factor Erythroid 2-Related Factor 2 Downstream of Phosphatidylinositol 3-Kinase during Muscle Differentiation. Am. J. Pathol. 172: 1529-1541 [Abstract] [Full Text]  
  • Kode, A., Rajendrasozhan, S., Caito, S., Yang, S.-R., Megson, I. L., Rahman, I. (2008). Resveratrol induces glutathione synthesis by activation of Nrf2 and protects against cigarette smoke-mediated oxidative stress in human lung epithelial cells. Am. J. Physiol. Lung Cell. Mol. Physiol. 294: L478-L488 [Abstract] [Full Text]  
  • Xing, W., Singgih, A., Kapoor, A., Alarcon, C. M., Baylink, D. J., Mohan, S. (2007). Nuclear Factor-E2-related Factor-1 Mediates Ascorbic Acid Induction of Osterix Expression via Interaction with Antioxidant-Responsive Element in Bone Cells. J. Biol. Chem. 282: 22052-22061 [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]  
  • Minsavage, G. D., Dillman, J. F. III (2007). Bifunctional Alkylating Agent-Induced p53 and Nonclassical Nuclear Factor {kappa}B Responses and Cell Death Are Altered by Caffeic Acid Phenethyl Ester: A Potential Role for Antioxidant/Electrophilic Response-Element Signaling. J. Pharmacol. Exp. Ther. 321: 202-212 [Abstract] [Full Text]  
  • Hock, T. D., Liby, K., Wright, M. M., McConnell, S., Schorpp-Kistner, M., Ryan, T. M., Agarwal, A. (2007). JunB and JunD Regulate Human Heme Oxygenase-1 Gene Expression in Renal Epithelial Cells. J. Biol. Chem. 282: 6875-6886 [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»