Disease relevance of Nfe2l1

• Although ROS are key effectors of neuronal death after ischaemic and traumatic brain injury, it is not known whether Nrf-1 and Nrf-2 are involved in neuroprotective signalling [1].
• Nrf2 determines the susceptibility of lungs to cigarette smoke-induced emphysema in mice through the transcriptional induction of numerous antioxidant genes [2].
• Analysis in mouse insulinoma MIN6 cells revealed that methoxyflavones mildly activated the eukaryotic initiation factor 2alpha and nuclear factor erythroid 2-related factor pathways, but not the XBP1 pathway, and induced downstream genes, including glucose-regulated protein (GRP) 78, a molecular chaperone in the ER [3].

High impact information on Nfe2l1

• Nine epithelial tumor cell lines that were derived from inbred C57BL/lcrf-at adult male mouse bladder and were transformed in vitro were cytogenetically analyzed [4].
• Three members, p45-Nf-e2, Nrf-1 and Nrf-2 have been identified in mammals [5].
• Homozygous Nrf-1 mutant mice are anemic due to a non-cell autonomous defect in definitive erythropoiesis and die in utero [5].
• A tissue culture cell line was established from an alveologenic lung carcinoma from a C57BL/lcrf-at mouse [6].
• NF-E2-related factor (Nrf) 2 protein, a transcription factor crucial for MRP1 gene expression, was similarly increased in the kidneys of both strains of mice after NaAs treatment [7].

Biological context of Nfe2l1

• Murine Nfe2l1 maps to chromosome 11DE with similar sequence at 7D1-7F1 and 2E4-2G [8].
• Upregulation and activation of the Nrf-1 transcription factor in the lesioned hippocampus [1].
• The transcription factor NF-E2-related factor (Nrf2) regulates the induction of phase 2 detoxifying enzymes by oxidative stress, including synthesis of the catalytic subunit (xCT) of the heterodimeric cystine-glutamate exchanger (system xc-) [9].
• Nrf2 gene deletion fails to alter psychostimulant-induced behavior or neurotoxicity [9].
• Nuclear factor erythroid 2-related factor (Nrf2) confers protection against cell death induced by hyperoxia and other proapoptotic stimuli [10].

Anatomical context of Nfe2l1

• Nrf-1 predominantly localized to the nucleus in the injured hippocampus [1].
• Nrf1 is targeted to the endoplasmic reticulum membrane by an N-terminal transmembrane domain. Inhibition of nuclear translocation and transacting function [11].

Associations of Nfe2l1 with chemical compounds

• Treatment with tunicamycin, an endoplasmic reticulum stress inducer, caused an accumulation of a smaller form of Nrf1 that correlated with detection of Nrf1 in the nucleus by biochemical fractionation and immunofluorescent analysis [11].
• The lungs of Nrf2-/- mice have higher oxidative stress as evident from the increased levels of lipid peroxidation (4-hydroxy-2-nonenal) and oxidative DNA damage (7,8-dihydro-8-Oxo-2'deoxyguanosine) in response to cigarette smoke [2].
• Glutathione Peroxidase 2, the Major Cigarette Smoke-Inducible Isoform of GPX in Lungs, Is Regulated by Nrf2 [2].

Other interactions of Nfe2l1

• NF-E2 related factor (Nrf2) controls a pleiotropic cellular defense, where multiple antioxidant/detoxification pathways are up-regulated in unison [12].

Analytical, diagnostic and therapeutic context of Nfe2l1

• The binding of Nrf2 to the GPX2 antioxidant response element was confirmed by chromatin immunoprecipation, electrophoretic mobility shift assays, and site-directed mutagenesis [2].

References