INT147471

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Context Info
Confidence 0.57
First Reported 2008
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 10
Total Number 16
Disease Relevance 4.18
Pain Relevance 1.43

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

plasma membrane (Nfe2l2) nucleus (Nfe2l2) DNA binding (Nfe2l2)
cytoplasm (Nfe2l2)
Anatomy Link Frequency
embryonic kidney 4
embryonic death 2
Nfe2l2 (Mus musculus)
Pain Link Frequency Relevance Heat
Antinociceptive 12 99.80 Very High Very High Very High
Analgesic 4 99.64 Very High Very High Very High
Glutamate 4 97.04 Very High Very High Very High
Pain 7 95.68 Very High Very High Very High
Morphine 1 93.88 High High
Inflammation 10 84.56 Quite High
cINOD 5 81.36 Quite High
IPN 6 75.00 Quite High
Paracetamol 17 74.72 Quite High
nociceptor 4 25.00 Low Low
Disease Link Frequency Relevance Heat
Toxicity 25 99.98 Very High Very High Very High
Stress 185 99.40 Very High Very High Very High
Death 10 98.68 Very High Very High Very High
Targeted Disruption 42 97.88 Very High Very High Very High
Pain 1 95.68 Very High Very High Very High
INFLAMMATION 8 84.56 Quite High
Cancer 43 82.96 Quite High
Nociception 6 81.40 Quite High
Esophageal Disease 1 80.76 Quite High
Ulcers 1 80.16 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
As expected, we found that endogenous CRIF1 knockdown allowed modest but statistically significant increased reporter activity after NRF2 overexpression and after t-BHQ exposure (Fig. 7A) as compared with cells containing normal amounts of CRIF1.
Positive_regulation (overexpression) of Gene_expression (overexpression) of NRF2
1) Confidence 0.57 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0 Pain Relevance 0
Thus, Keap1 knock-out mice die shortly after birth (possibly from uncontrolled expression of Nrf2 target genes), but mice defective for both Keap1 and Nrf2 are viable (possibly because Nrf2 target genes cannot be overexpressed sufficiently to cause embryonic death in the double knock-out).
Positive_regulation (overexpressed) of Neg (cannot) Gene_expression (overexpressed) of Nrf2 in embryonic death associated with targeted disruption and death
2) Confidence 0.57 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.89 Pain Relevance 0
However, under these conditions, this AP-1 mutant did not limit the ability of overexpressed NRF2 (Fig. 6B, middle panel) to induce reporter activity, but it may somewhat limit the capacity of t-BHQ treatment to induce reporter activity (Fig. 6C, middle panel).
Positive_regulation (overexpressed) of Gene_expression (overexpressed) of NRF2
3) Confidence 0.57 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.15 Pain Relevance 0
The genomic enhancer of HO-1 can be induced under both reducing conditions (by overexpressing NRF2) and under oxidative stress (t-BHQ).
Positive_regulation (overexpressing) of Gene_expression (overexpressing) of NRF2 associated with stress
4) Confidence 0.57 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.32 Pain Relevance 0
Human embryonic kidney (HEK) 293T cells treated with 10 microM CoPP expressed 20-fold higher HO-1 levels when compared to controls; this effect was suppressed by transfection with the dominant negative for the nuclear factor-erythroid 2-related factor 2 (Nrf2).
Positive_regulation (transfection) of Gene_expression (transfection) of nuclear factor-erythroid 2-related factor 2 in embryonic kidney
5) Confidence 0.48 Published 2008 Journal Pain Section Abstract Doc Link 17964723 Disease Relevance 0.53 Pain Relevance 0.17
Human embryonic kidney (HEK) 293T cells treated with 10 microM CoPP expressed 20-fold higher HO-1 levels when compared to controls; this effect was suppressed by transfection with the dominant negative for the nuclear factor-erythroid 2-related factor 2 (Nrf2).
Positive_regulation (transfection) of Gene_expression (transfection) of Nrf2 in embryonic kidney
6) Confidence 0.48 Published 2008 Journal Pain Section Abstract Doc Link 17964723 Disease Relevance 0.53 Pain Relevance 0.17
In summary, this study has identified a panel of Nrf2-dependent hepatic proteins that is statistically robust and demonstrated both decreased and enhanced expression in the absence of the Nrf2 gene.
Positive_regulation (enhanced) of Gene_expression (expression) of Nrf2
7) Confidence 0.47 Published 2010 Journal Journal of Proteomics Section Body Doc Link PMC2891861 Disease Relevance 0 Pain Relevance 0
Haeme oxygenase-1 overexpression via nAChRs and the transcription factor Nrf2 has antinociceptive effects in the formalin test.
Positive_regulation (overexpression) of Gene_expression (overexpression) of Nrf2 associated with analgesic and antinociceptive
8) Confidence 0.46 Published 2009 Journal Pain Section Title Doc Link 19660867 Disease Relevance 0.31 Pain Relevance 0.49
OA treatment dramatically increased expression of hepatic metallothionein (Mt), and increased the expression of the nuclear factor E2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase-1 (Hmox1), and glutamate-cysteine ligases (Gclc and Gclm).
Positive_regulation (increased) of Gene_expression (expression) of nuclear factor E2-related factor 2 associated with glutamate
9) Confidence 0.46 Published 2008 Journal Biochem. Pharmacol. Section Abstract Doc Link 18706400 Disease Relevance 0 Pain Relevance 0.12
OA treatment dramatically increased expression of hepatic metallothionein (Mt), and increased the expression of the nuclear factor E2-related factor 2 (Nrf2), NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase-1 (Hmox1), and glutamate-cysteine ligases (Gclc and Gclm).
Positive_regulation (increased) of Gene_expression (expression) of Nrf2 associated with glutamate
10) Confidence 0.46 Published 2008 Journal Biochem. Pharmacol. Section Abstract Doc Link 18706400 Disease Relevance 0 Pain Relevance 0.12
Therefore, our data suggest that modulation of p65 has an effect on the ability of the cell to defend against toxicity via the Nrf2/Keap1 pathway, and that the Nrf2 and NF-?
Positive_regulation (via) of Gene_expression (pathway) of Nrf2 associated with toxicity
11) Confidence 0.41 Published 2010 Journal Biochemical Pharmacology Section Body Doc Link PMC2884179 Disease Relevance 0.48 Pain Relevance 0
Next, we identified sites in the HO-1 enhancer necessary for maximal reporter plasmid induction under either reducing (NRF2 overexpression) or oxidative stress-inducing conditions (t-BHQ) (Fig. 6).
Positive_regulation (overexpression) of Gene_expression (overexpression) of NRF2 associated with stress
12) Confidence 0.38 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.24 Pain Relevance 0
Following t-BHQ (or SFN), we found that exogenously expressed NRF2 levels increased, which may be due to the inhibition of NRF2 negative regulators, such as KEAP1.


Positive_regulation (increased) of Gene_expression (expressed) of NRF2
13) Confidence 0.38 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.06 Pain Relevance 0
Next, we identified sites in the HO-1 enhancer necessary for maximal reporter plasmid induction under either reducing (NRF2 overexpression) or oxidative stress-inducing conditions (t-BHQ) (Fig. 6).
Positive_regulation (induction) of Gene_expression (overexpression) of NRF2 associated with stress
14) Confidence 0.38 Published 2010 Journal The Journal of Biological Chemistry Section Body Doc Link PMC2898415 Disease Relevance 0.24 Pain Relevance 0
Eupatilin-induced HO-1 expression and Nrf2 were partly attenuated by MEK inhibitor PD98059 and almost completely by phosphatidyl-inactiol 3 kinase (PI3K) inhibitor LY294002, but not by c-Jun N-terminal kinase (JNK) inhibitor SP600125 or p38 mitogen activated protein kinase (MAPK) inhibitor SB202190.
Positive_regulation (induced) of Gene_expression (expression) of Nrf2
15) Confidence 0.13 Published 2009 Journal Biol. Pharm. Bull. Section Abstract Doc Link 19336889 Disease Relevance 0.30 Pain Relevance 0.29
We also found that PD98059, a MEK (MAPK/ERK kinase) inhibitor, attenuated the eupatilin-induced HO-1 expression and nuclear translocation of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2).
Positive_regulation (eupatilin-induced) of Gene_expression (expression) of Nrf2
16) Confidence 0.12 Published 2008 Journal J Ethnopharmacol Section Abstract Doc Link 18440740 Disease Relevance 0.14 Pain Relevance 0.07

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