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Gene Review

Nfe2l2  -  nuclear factor, erythroid 2-like 2

Rattus norvegicus

Synonyms: NF-E2-related factor 2, NFE2-related factor 2, Nrf2, Nuclear factor erythroid 2-related factor 2, Nuclear factor, erythroid derived 2, like 2
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Disease relevance of Nfe2l2


High impact information on Nfe2l2

  • Because nuclear factor erythroid2-related factor 2 (Nrf2) governs basal and inducible GCLC and GCLM expression by means of the antioxidant response element (ARE), we hypothesized that aging results in dysregulation of Nrf2-mediated GCL expression [2].
  • Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid [2].
  • The present study investigated the repressing effects of activating glucocorticoid receptor (GR) on C/EBPbeta- and Nrf2-mediated GSTA2 gene induction and the mechanism [3].
  • The expression of the glutathione S-transferase gene (GST), whose induction accounts for cancer chemoprevention, is regulated by activation of CCAAT/enhancer binding protein beta (C/EBPbeta) and NF-E2-related factor 2 (Nrf2) [3].
  • Both Nrf2 and HO-1 levels were increased and co-localized with reactive astrocytes in the degenerating lumbar spinal cord of rats expressing the amyotrophic lateral sclerosis-linked SOD1 G93A mutation [4].

Biological context of Nfe2l2


Anatomical context of Nfe2l2


Associations of Nfe2l2 with chemical compounds

  • Dexamethasone-GR activation did not inhibit nuclear translocation of C/EBPbeta or Nrf2 nor their DNA binding activities induced by oltipraz or t-BHQ [3].
  • Coordinate regulation of glutathione metabolism in astrocytes by Nrf2 [11].
  • In addition, we show that the redox-sensitive transcription factor Nrf2 is highly expressed in the nuclear fraction of cells exposed to the NO- generator and that this effect is totally abolished by the presence of N-acetyl-L-cysteine [12].
  • 4-Hydroxynonenal induces adaptive response and enhances PC12 cell tolerance primarily through induction of thioredoxin reductase 1 via activation of Nrf2 [13].
  • The current study was designed to investigate the role of peroxynitrite in Nrf2/ARE activation and rGSTA2 induction [14].
  • CO produced by HO-1 rescues PC12 cells from nitrosative stress through induction of GCLC, which is mediated by activation of phosphatidylinositol 3-kinase/Akt and subsequently Nrf2 signaling [15].

Other interactions of Nfe2l2


Analytical, diagnostic and therapeutic context of Nfe2l2


  1. Regulation of GST-P gene expression during hepatocarcinogenesis. Sakai, M., Muramatsu, M. Meth. Enzymol. (2005) [Pubmed]
  2. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Suh, J.H., Shenvi, S.V., Dixon, B.M., Liu, H., Jaiswal, A.K., Liu, R.M., Hagen, T.M. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  3. Glucocorticoid receptor (GR)-associated SMRT binding to C/EBPbeta TAD and Nrf2 Neh4/5: role of SMRT recruited to GR in GSTA2 gene repression. Ki, S.H., Cho, I.J., Choi, D.W., Kim, S.G. Mol. Cell. Biol. (2005) [Pubmed]
  4. Fibroblast growth factor-1 induces heme oxygenase-1 via nuclear factor erythroid 2-related factor 2 (Nrf2) in spinal cord astrocytes: consequences for motor neuron survival. Vargas, M.R., Pehar, M., Cassina, P., Martínez-Palma, L., Thompson, J.A., Beckman, J.S., Barbeito, L. J. Biol. Chem. (2005) [Pubmed]
  5. Endoplasmic reticulum stress stimulates heme oxygenase-1 gene expression in vascular smooth muscle. Role in cell survival. Liu, X.M., Peyton, K.J., Ensenat, D., Wang, H., Schafer, A.I., Alam, J., Durante, W. J. Biol. Chem. (2005) [Pubmed]
  6. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. McMahon, M., Itoh, K., Yamamoto, M., Hayes, J.D. J. Biol. Chem. (2003) [Pubmed]
  7. Heme activates the heme oxygenase-1 gene in renal epithelial cells by stabilizing Nrf2. Alam, J., Killeen, E., Gong, P., Naquin, R., Hu, B., Stewart, D., Ingelfinger, J.R., Nath, K.A. Am. J. Physiol. Renal Physiol. (2003) [Pubmed]
  8. Phosphatidylinositol 3-kinase regulates nuclear translocation of NF-E2-related factor 2 through actin rearrangement in response to oxidative stress. Kang, K.W., Lee, S.J., Park, J.W., Kim, S.G. Mol. Pharmacol. (2002) [Pubmed]
  9. Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells. Chen, C.Y., Jang, J.H., Li, M.H., Surh, Y.J. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  10. Induction of Rat UDP-Glucuronosyltransferases in Liver and Duodenum by Microsomal Enzyme Inducers That Activate Various Transcriptional Pathways. Shelby, M.K., Klaassen, C.D. Drug Metab. Dispos. (2006) [Pubmed]
  11. Coordinate regulation of glutathione metabolism in astrocytes by Nrf2. Sun, X., Erb, H., Murphy, T.H. Biochem. Biophys. Res. Commun. (2005) [Pubmed]
  12. Interaction of heme with nitroxyl or nitric oxide amplifies heme oxygenase-1 induction: involvement of the transcription factor Nrf2. Naughton, P., Hoque, M., Green, C.J., Foresti, R., Motterlini, R. Cell. Mol. Biol. (Noisy-le-grand) (2002) [Pubmed]
  13. 4-Hydroxynonenal induces adaptive response and enhances PC12 cell tolerance primarily through induction of thioredoxin reductase 1 via activation of Nrf2. Chen, Z.H., Saito, Y., Yoshida, Y., Sekine, A., Noguchi, N., Niki, E. J. Biol. Chem. (2005) [Pubmed]
  14. Peroxynitrite activates NF-E2-related factor 2/antioxidant response element through the pathway of phosphatidylinositol 3-kinase: the role of nitric oxide synthase in rat glutathione S-transferase A2 induction. Kang, K.W., Choi, S.H., Kim, S.G. Nitric Oxide (2002) [Pubmed]
  15. Carbon monoxide produced by heme oxygenase-1 in response to nitrosative stress induces expression of glutamate-cysteine ligase in PC12 cells via activation of phosphatidylinositol 3-kinase and Nrf2 signaling. Li, M.H., Jang, J.H., Na, H.K., Cha, Y.N., Surh, Y.J. J. Biol. Chem. (2007) [Pubmed]
  16. Flavonoids protect retinal ganglion cells from oxidative stress-induced death. Maher, P., Hanneken, A. Invest. Ophthalmol. Vis. Sci. (2005) [Pubmed]
  17. Zerumbone, a tropical ginger sesquiterpene, activates phase II drug metabolizing enzymes. Nakamura, Y., Yoshida, C., Murakami, A., Ohigashi, H., Osawa, T., Uchida, K. FEBS Lett. (2004) [Pubmed]
  18. 4-Hydroxynonenal induces rat gamma-glutamyl transpeptidase through mitogen-activated protein kinase-mediated electrophile response element/nuclear factor erythroid 2-related factor 2 signaling. Zhang, H., Liu, H., Iles, K.E., Liu, R.M., Postlethwait, E.M., Laperche, Y., Forman, H.J. Am. J. Respir. Cell Mol. Biol. (2006) [Pubmed]
  19. Comparative study of PM2.5 - and PM10 - induced oxidative stress in rat lung epithelial cells. Choi, J.H., Kim, J.S., Kim, Y.C., Kim, Y.S., Chung, N.H., Cho, M.H. J. Vet. Sci. (2004) [Pubmed]
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