Nuclear factor erythroid-2-related factor 2 (Nrf2) is a transcription factor that is upregulated in times of oxidative stress. (hindawi.com)
The multifunctional regulator nuclear factor erythroid 2-related factor (Nrf2) is considered not only as a cytoprotective factor regulating the expression of genes coding for anti-oxidant, anti-inflammatory and detoxifying proteins, but it is also a powerful modulator of species longevity. (springer.com)
Keap111
This review focuses on the effects of oxidative stress and the role of a particular antioxidant system-the Keap1-Nrf2-ARE pathway-on ocular diseases, specifically age-related macular degeneration, cataracts, diabetic retinopathy, and glaucoma. (hindawi.com)
The Keap1-Nrf2-ARE pathway plays a critical role in the regulation of a comprehensive and protective antioxidant response [ 22 ]. (hindawi.com)
As shown in Figure 1 , in the absence of oxidative stress, Kelch-like ECH-associated protein 1 (Keap1) keeps Nrf2 sequestered in the cytosol, where it mediates proteasomal degradation of Nrf2 [ 25 - 27 ]. (hindawi.com)
Upon exposure to ROS, Keap1 undergoes a conformational change that allows Nrf2 to translocate to the nucleus, bind to the ARE region, and initiate transcription of target genes [ 24 ]. (hindawi.com)
Under nonstressed conditions, Keap1 keeps Nrf2 sequestered in the cytosol, where it mediates proteasomal degradation of Nrf2. (hindawi.com)
Under oxidative-stressed conditions, cysteine residues of Keap1 are oxidized, forming a disulfide bridge. (hindawi.com)
Oxidized Keap1 dissociates from Nrf2, allowing Nrf2 to translocate to the nucleus, bind to the ARE region, and initiate transcription of target genes. (hindawi.com)
Nrf2 consists of six functional Neh domains (Neh1-Neh6), from which, the amino-terminal Neh2 domain controls binding Keap1-the inhibitor protein Kelch-like ECH-associated protein 1, that is responsible for the cytosolic sequestration of Nrf2 under physiological conditions (Fig. 2 a). (springer.com)
Keap1 is a cysteine-rich protein, known to be anchored to actin cytoskeleton [ 5 ], serving as an adaptor protein for the Cul3-dependent E3 ubiquitin ligase complex. (springer.com)
Under normal conditions, Keap1 promotes ubiquitination and eventual degradation of Nrf2. (springer.com)
fumarate was found to covalently improve cysteine residues of Keap1, the bad regulator of the transcription element Nrf2, suggesting a part for a deregulated antioxidant response in the formation of FH-deficient tumors [8,9]. (immune-source.com)
Oxidative stress2
Proposed molecular mechanisms of oxidative stress-induced Nrf2 activation. (hindawi.com)
PGJ abrogates liver fibrosis instigated by NDEA in Wistar rats by declining oxidative stress via regulation of Nrf2 and NFκB. (nature.com)
Activates1
Nrf2 activates transcription of antioxidant enzymes by binding to the antioxidant response element (ARE) in the promoter regions of its target genes [ 23 , 24 ]. (hindawi.com)
Transcription2
Nrf2 is a master eukaryotic redox-active factor and belongs to Cap 'n' Collar (Cnc)-bZIP (basic leucine zipper) family of transcription factors. (springer.com)
Nrf2 stabilization and increase in its half-life even to 200 min [ 9 ] allows nuclear translocation and activation of transcription of cytoprotective genes (Fig. 1 ). (springer.com)
Antioxidant2
Both "direct" and "indirect" antioxidant enzymes are regulated by Nrf2. (hindawi.com)
The discovery of the antioxidant response element (ARE) have led to the conclusion that the battery of genes, including glutamate-cysteine ligase (GCL), thioredoxin reductase 1 (Txnrd1), NAD(P)H-quinone oxidoreductase 1 (NQO1) and heme oxygenase-1 (HMOX1) is regulated through Nrf2 binding to this consensus binding sequence [ 3 ]. (springer.com)
Proteins2
The major characteristics of Nrf2 are to some extent mimicked by Nrf2-dependent genes and their proteins including heme oxygenase-1 (HO-1), which besides removing toxic heme, produces biliverdin, iron ions and carbon monoxide. (springer.com)
Membrane embedded proteins are functionally regulated by the lipid composition of the surrounding bilayer. (sphingolipidclub.com)
Inflammation1
Sphingosine 1-phosphate (S1P) is a pleiotropic bioactive sphingolipid metabolite that regulates numerous processes important for inflammation and cancer. (sphingolipidclub.com)
Adaptive1
Interestingly, a recent study reported that topical appli- mation, ACD critically depends on adaptive immunity. (cdc.gov)
Role1
This review summarizes our knowledge about Nrf2 and HO-1 across different phyla suggesting their conservative role as stress-protective and anti-aging factors. (springer.com)
The findings demonstrate for the first time that Nrf2 cysteine residues critically regulate oxidant/eletrophile sensing, repress Keap1-dependent ubiquitination-proteasomal degradation, and promote recruitment of co-activators, such that chemical sensing, receptor activation, and transcription activation are integrated at the receptor molecule. (cdc.gov)
NRF2 cysteine residues are critical for oxidant/electrophile-sensing, Kelch-like ECH-associated protein-1-dependent ubiquitination-proteasomal degradation, and transcription activation. (cdc.gov)
Regulation4
Here we show that evolutionally conserved cysteine residues of Nrf2 are critical for Nrf2 regulation. (cdc.gov)
To corroborate the functions of cysteine residues, Nrf2 wild-type or mutants are expressed in Nrf2 knockout cells to reconstitute Nrf2 regulation. (cdc.gov)
However, the role of metabolic regulation in Nrf2-mediated anti-ROS pathway and the pathogenesis of DKD is still unclear. (researchsquare.com)
The DDIT4 gene, encoding the DNA-damage-inducible transcript 4, associated with regulation and development of DNA processes after damage by ionizing radiation and in p53 mediated apoptotic processes, is up-regulated. (ijpsr.com)
Degradation1
Activation involves blocking the ubiquitination-proteasomal degradation of Nrf2. (cdc.gov)
Genes2
FlAsH (an arsenic-based fluorophore) and phenylarsine oxide (PAO) potently induce Nrf2 target genes and bind to Nrf2 in vitro and in vivo. (cdc.gov)
After 24 hours, a return back to normal was not observed and the genes remained stably down-regulated. (ijpsr.com)
Mitochondrial1
Mitochondrial mass and quality are tightly regulated by two essential and opposing mechanisms, mitochondrial biogenesis (mitobiogenesis) and mitophagy, in response to cellular energy needs and other cellular and environmental cues. (biomedcentral.com)
Activation3
Remarkably, the mutants fail to respond to arsenic for Nrf2 activation and gene in- duction. (cdc.gov)
It is remarkable that the mutants fail to respond to arsenic for Nrf2 activation and gene induction. (cdc.gov)
Proposed molecular mechanisms of oxidative stress-induced Nrf2 activation. (hindawi.com)
Nuclear factor1
Reactive oxygen species (ROS) levels, nuclear factor red 2-related factor 2 (Nrf2) protein expression, and βOHB-acetoacetate (AcAc)-succinate-fumarate metabolic flux were detected. (researchsquare.com)
Critical2
PAO affin- ity pulldown and mutation of individual cysteine to alanine reveal that C235, C311, C316, C414 and C506 are critical for binding and binding is modulated by intra-molecular interactions. (cdc.gov)
PAO affinity pull-down and mutation of individual cysteine to alanine reveal that Cys235, Cys311, Cys316, Cys414, and Cys506 are critical for binding, and binding is modulated by intramolecular interactions. (cdc.gov)
Factor1
ID1, inhibitor of DNA binding, are up-regulated as a rapid response after 2 h with a factor 3.8 and RPS2, ribosomal protein S2 , is down-regulated to nearly 50 % after 24 hours. (ijpsr.com)
Cells1
The renal expression of Bdh1 was down-regulated in DKD mouse models, diabetic patients and HG or PA induced HK-2 cells. (researchsquare.com)