INT197568

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Context Info
Confidence 0.59
First Reported 2006
Last Reported 2010
Negated 4
Speculated 2
Reported most in Body
Documents 17
Total Number 19
Disease Relevance 7.85
Pain Relevance 0.15

This is a graph with borders and nodes. Maybe there is an Imagemap used so the nodes may be linking to some Pages.

cytosol (NFE2L2) plasma membrane (NFE2L2) nucleus (NFE2L2)
DNA binding (NFE2L2) cytoplasm (NFE2L2)
Anatomy Link Frequency
hinge 1
NFE2L2 (Homo sapiens)
Pain Link Frequency Relevance Heat
Inflammation 60 94.08 High High
tolerance 1 84.16 Quite High
antagonist 4 58.12 Quite High
fibrosis 3 44.52 Quite Low
cytokine 16 38.84 Quite Low
Glutamate 9 29.32 Quite Low
metalloproteinase 12 9.04 Low Low
chemokine 10 5.00 Very Low Very Low Very Low
Inflammatory response 8 5.00 Very Low Very Low Very Low
Paracetamol 7 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Cancer 689 99.84 Very High Very High Very High
Nicotine Addiction 67 98.40 Very High Very High Very High
Pulmonary Disease 99 96.80 Very High Very High Very High
Toxicity 112 96.64 Very High Very High Very High
Emphysema 31 96.16 Very High Very High Very High
Non-small-cell Lung Cancer 144 95.76 Very High Very High Very High
INFLAMMATION 65 94.08 High High
Asthma 3 93.40 High High
Carcinoma 6 90.52 High High
Stress 118 89.48 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Incubation of anti-NRF2 antibody with NRF2 protein dramatically reduced the staining, whereas incubation with luciferase protein had no effect on NRF2 antibody staining (Figure S3).
Neg (no) Regulation (effect) of NRF2
1) Confidence 0.59 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.79 Pain Relevance 0
Keap1-null mutation in mice results in postnatal lethality because of constitutive Nrf2 activation, whereas heterozygous mutation of Keap1 has no effect on Nrf2 activity [23].
Neg (no) Regulation (effect) of Nrf2
2) Confidence 0.59 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.15 Pain Relevance 0
These results demonstrate that oridonin is able to induce the Nrf2 signaling pathway mainly through up-regulation of Nrf2 at the protein level.


Regulation (regulation) of Nrf2
3) Confidence 0.45 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.05 Pain Relevance 0
Therefore, we tested the ability of oridonin in modulating Nrf2 ubiquitination.
Regulation (modulating) of Nrf2
4) Confidence 0.45 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
Up-regulation of the Nrf2-dependent defense response has proved to be beneficial in reducing arsenic-induced toxicity in a cell culture model (Wang et al. 2007).
Regulation (regulation) of Nrf2 associated with toxicity
5) Confidence 0.45 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.25 Pain Relevance 0
Thus, a heterozygous mutation in KEAP1, as reported recently [24], may not effect NRF2-mediated cytoprotective gene expression.
Neg (not) Spec (may) Regulation (effect) of NRF2
6) Confidence 0.43 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.12 Pain Relevance 0
The “hinge and latch” model of Nrf2 regulation proposes that two distinct binding sites in Nrf2 facilitate the interaction with a Keap1 dimer (8).
Spec (proposes) Regulation (regulation) of Nrf2 in hinge
7) Confidence 0.33 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2878012 Disease Relevance 0.38 Pain Relevance 0
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical regulator of the cellular antioxidant response and xenobiotic metabolism.
Regulation (regulator) of Nrf2
8) Confidence 0.27 Published 2008 Journal Environ Health Perspect Section Abstract Doc Link PMC2535615 Disease Relevance 0.23 Pain Relevance 0
Furthermore, we demonstrated the feasibility of using natural compounds targeting Nrf2 as a therapeutic approach to protect humans from various environmental insults that may occur daily.



Regulation (targeting) of Nrf2
9) Confidence 0.27 Published 2008 Journal Environ Health Perspect Section Abstract Doc Link PMC2535615 Disease Relevance 0.21 Pain Relevance 0
We also studied levels of known NRF2 targets in tumor samples by measuring NQO1 and GST enzyme activities and total GSH levels in 13 pairs of primary NSCLC tumors and adjacent normal tissues.
Regulation (targets) of NRF2 associated with non-small-cell lung cancer and cancer
10) Confidence 0.26 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.81 Pain Relevance 0
The Kelch repeats of KEAP1 bind the Neh2 domain of NRF2, whereas the IVR and BTB domains are required for the redox-sensitive regulation of NRF2 through a series of reactive cysteines present throughout this region [22].
Regulation (regulation) of NRF2
11) Confidence 0.26 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.50 Pain Relevance 0
The siRNA sequence targeting NRF2 corresponds to the coding region nucleotides 1903–1921 (5?
Regulation (targeting) of NRF2
12) Confidence 0.26 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0 Pain Relevance 0
SQSTM1 was dispensable for the induction of the Keap1-Nrf2 pathway, as Nrf2 activation by tert-butylhydroquinone or iodoacetamide was not affected by RNAi depletion of SQSTM1.
Neg (not) Regulation (affected) of Nrf2
13) Confidence 0.24 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878012 Disease Relevance 0 Pain Relevance 0
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical transcription factor that regulates a cytoprotective response.
Regulation (regulates) of factor 2
14) Confidence 0.24 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.38 Pain Relevance 0
The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) is a critical regulator of the cellular antioxidant response and xenobiotic metabolism.
Regulation (regulator) of factor 2
15) Confidence 0.24 Published 2008 Journal Environ Health Perspect Section Abstract Doc Link PMC2535615 Disease Relevance 0.23 Pain Relevance 0
The response observed in the present study may therefore be considered as adaptive occurring before the triggering of protective antioxidant/xenobiotic enzyme expression under the regulation of Nrf2 [47,57].
Regulation (regulation) of Nrf2
16) Confidence 0.23 Published 2010 Journal Part Fibre Toxicol Section Body Doc Link PMC2936868 Disease Relevance 0.36 Pain Relevance 0.08
Furthermore, RNA interference (RNAi) depletion of SQSTM1 resulted in an increase in the protein level of Keap1 and a concomitant decrease in the protein level of Nrf2 in the absence of changes in Keap1 or Nrf2 mRNA levels.
Regulation (changes) of Nrf2 mRNA
17) Confidence 0.15 Published 2010 Journal The Journal of Biological Chemistry Section Abstract Doc Link PMC2878012 Disease Relevance 0 Pain Relevance 0
Genetic ablation of Nrf2, a pivotal transcriptional factor regulating the expression of many antioxidant enzymes, enhances susceptibility to cigarette smoke-induced emphysema (Rangasamy et al 2004), and severe airway inflammation and asthma in mice (Rangasamy et al 2005).
Regulation (regulating) of Nrf2 associated with asthma, emphysema and inflammation
18) Confidence 0.11 Published 2008 Journal International Journal of Chronic Obstructive Pulmonary Disease Section Body Doc Link PMC2629979 Disease Relevance 1.19 Pain Relevance 0.08
Since Keap1 is involved in regulation of the activity of the Nrf2 transcription factor that directs Phase 2 gene transcription from the promoter element termed the antioxidant response element (ARE), Keap1 is an attractive potential target for ITCs.
Regulation (regulation) of Nrf2
19) Confidence 0.04 Published 2007 Journal BMC Cancer Section Body Doc Link PMC2071920 Disease Relevance 0.19 Pain Relevance 0

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