Disease relevance of Nfe2l2

• Electrophoresis gel mobility shift assay, reporter transfection analysis, and the chromatin immunoprecipitation analysis indicate that the Nrf2/MafK heterodimer binds and activates GPE1 element in preneoplastic lesions and hepatomas but not in the normal liver cells [1].

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

• Overexpression of Nrf2 in astrocytes increased survival of co-cultured embryonic motor neurons and prevented motor neuron apoptosis mediated by nerve growth factor through p75 neurotrophin receptor [4].
• Moreover, ER stress induced the nuclear import of Nrf2 and the binding of Nrf2 to the HO-1 antioxidant response element [5].
• In the RL34 non-transformed rat liver cell line, Nrf2 was found to accumulate rapidly in response to oxidative stress caused by treatment with sulforaphane, and the accumulation resulted from inhibition of proteasomal-mediated degradation of the bZIP protein [6].
• Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression [6].
• Heme did not affect the transcription activity of Nrf2, dimerization between Nrf2 and MafG, or the level of MafG, but did stimulate expression of Nrf2 [7].

Anatomical context of Nfe2l2

• In contrast, phalloidin, an agent that prevents actin filaments from depolymerization, inhibited Nrf2 translocation and rGSTA2 induction by t-BHQ [8].
• Heme activates the heme oxygenase-1 gene in renal epithelial cells by stabilizing Nrf2 [7].
• Resveratrol upregulates heme oxygenase-1 expression via activation of NF-E2-related factor 2 in PC12 cells [9].
• Nrf2 activators increased UGT2B3 and 2B12 in both liver and duodenum, and UGT1A6, 1A7, and 2B1 in liver only [10].

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

• Keap1 is a negative regulator of Nrf2, a bZIP transcription factor that mediates adaptation to oxidative stress [6].
• Several of the protective flavonoids also induced the synthesis of the transcription factor NF-E2-related factor 2 and phase 2 antioxidant enzymes such as heme oxygenase 1, markers for the activation of the antioxidant response element [16].
• This is consistent with the observation that ZER potentiated the gene expression of several Nrf2/ARE-dependent phase II enzyme genes, including gamma-glutamylcysteine synthetase, glutathione peroxidase, and hemeoxygenase-1 [17].
• Immunoblot and immunoprecipitation assays showed that the 100-kDa protein comprised both Nrf2 and actin [8].
• Dominant-negative mutants of Nrf2 and Maf, but not of c-Fos and c-Jun, inhibited basal and heme-induced expression of an E1-controlled luciferase gene [7].

Analytical, diagnostic and therapeutic context of Nfe2l2

• Electrophoretic mobility shift assays identified Nrf2, MafG, ATF3, and Jun and Fos family members as StRE-binding proteins; binding of Nrf2, MafG, and ATF3 was increased in response to heme [7].
• HNE-induced binding of Nrf2 and c-Jun in GP5 EpRE was confirmed by chromatin immunoprecipitation assays [18].
• In Western blot analysis, PM2.5 induced more Nrf-2 protein, associated with diverse transcriptional and anti-oxidative stress enzymes, compared to PM10 [19].

References