INT118390

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Context Info
Confidence 0.70
First Reported 2004
Last Reported 2010
Negated 0
Speculated 1
Reported most in Abstract
Documents 82
Total Number 83
Disease Relevance 20.41
Pain Relevance 10.61

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
hepatocytes 5
liver 4
macrophages 1
fat 1
brain 1
Nfe2l2 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammation 195 100.00 Very High Very High Very High
Analgesic 29 100.00 Very High Very High Very High
Pain 3 100.00 Very High Very High Very High
nociceptor 2 100.00 Very High Very High Very High
Paracetamol 213 99.90 Very High Very High Very High
qutenza 13 98.88 Very High Very High Very High
Glutamate 43 98.64 Very High Very High Very High
Antinociceptive 3 98.48 Very High Very High Very High
dexamethasone 6 98.32 Very High Very High Very High
IPN 3 97.20 Very High Very High Very High
Disease Link Frequency Relevance Heat
Stress 900 100.00 Very High Very High Very High
Injury 138 99.92 Very High Very High Very High
Congenital Anomalies 6 99.72 Very High Very High Very High
INFLAMMATION 243 99.56 Very High Very High Very High
Toxicity 426 99.32 Very High Very High Very High
Targeted Disruption 214 98.32 Very High Very High Very High
Aging 26 97.68 Very High Very High Very High
Hepatotoxicity 49 97.48 Very High Very High Very High
Inflammatory Pain 3 97.20 Very High Very High Very High
Cancer 176 96.96 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Transcription factor NF-E2-related factor 2 (Nrf2) belongs to the basic region-leucine zipper family and is activated in response to electrophiles and reactive oxygen species.
Positive_regulation (activated) of Nrf2
1) Confidence 0.70 Published 2007 Journal Toxicol Pathol Section Abstract Doc Link 17562481 Disease Relevance 0.15 Pain Relevance 0
Transcription factor NF-E2-related factor 2 (Nrf2) belongs to the basic region-leucine zipper family and is activated in response to electrophiles and reactive oxygen species.
Positive_regulation (activated) of NF-E2-related factor 2
2) Confidence 0.70 Published 2007 Journal Toxicol Pathol Section Abstract Doc Link 17562481 Disease Relevance 0.15 Pain Relevance 0
To investigate acetaminophen-induced Nrf2 activation we compared the actions of 2 other GSH depleters, diethyl maleate (DEM) and buthionine sulphoximine (BSO), only 1 of which (DEM) can function as a Michael acceptor.
Positive_regulation (activation) of Nrf2 associated with paracetamol
3) Confidence 0.70 Published 2004 Journal Hepatology Section Abstract Doc Link 15122755 Disease Relevance 0.20 Pain Relevance 0.42
Increased nuclear Nrf2 was found to be associated with depletion of hepatic GSH.
Positive_regulation (Increased) of Nrf2
4) Confidence 0.70 Published 2004 Journal Hepatology Section Abstract Doc Link 15122755 Disease Relevance 0.24 Pain Relevance 0.45
Activation of Nrf2 is considered to involve dissociation from a cytoplasmic inhibitor, Kelch-like ECH-associated protein 1 (Keap1), through a redox-sensitive mechanism involving either GSH depletion or direct chemical interaction through Michael addition.
Positive_regulation (Activation) of Nrf2
5) Confidence 0.70 Published 2004 Journal Hepatology Section Abstract Doc Link 15122755 Disease Relevance 0.23 Pain Relevance 0.44
Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 mice.
Positive_regulation (Activation) of Nrf2 associated with paracetamol
6) Confidence 0.70 Published 2004 Journal Hepatology Section Title Doc Link 15122755 Disease Relevance 0.26 Pain Relevance 0.43
In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH.
Positive_regulation (activation) of Nrf2
7) Confidence 0.70 Published 2004 Journal Hepatology Section Abstract Doc Link 15122755 Disease Relevance 0.06 Pain Relevance 0.30
Moreover, induction of the Nrf2 signaling pathway is essential for many food phytochemicals to exert their cancer chemopreventive activity as demonstrated in many preclinical studies.
Positive_regulation (induction) of Nrf2 associated with cancer
8) Confidence 0.69 Published 2008 Journal Planta Med. Section Abstract Doc Link 18937168 Disease Relevance 0.74 Pain Relevance 0.35
In conclusion, these data indicate that nimesulide is bioactivated by CYP2C to a protein-reactive electrophilic intermediate that activates the Nrf2 pathway even at nontoxic exposure levels.
Positive_regulation (activates) of Nrf2
9) Confidence 0.69 Published 2010 Journal Chem. Res. Toxicol. Section Abstract Doc Link 20405857 Disease Relevance 0.46 Pain Relevance 0
However, substantial depletion of glutathione (to less than 15% of basal levels) by buthionine sulfoximine, which does not directly modify Keap1, is also sufficient to activate Nrf2.
Positive_regulation (activate) of Nrf2
10) Confidence 0.69 Published 2008 Journal Hepatology Section Abstract Doc Link 18785192 Disease Relevance 0.06 Pain Relevance 0.25
The hepatotoxic metabolite of acetaminophen directly activates the Keap1-Nrf2 cell defense system.
Positive_regulation (activates) of Nrf2 associated with paracetamol
11) Confidence 0.69 Published 2008 Journal Hepatology Section Title Doc Link 18785192 Disease Relevance 0.16 Pain Relevance 0.30
It is possible that both of these mechanisms contribute to the activation of Nrf2 by acetaminophen.
Positive_regulation (activation) of Nrf2 associated with paracetamol
12) Confidence 0.69 Published 2008 Journal Hepatology Section Abstract Doc Link 18785192 Disease Relevance 0 Pain Relevance 0.21
CONCLUSION: Nrf2 can be activated via the direct modification of cysteine residues located within the intervening region of Keap1, but also via the substantial depletion of glutathione without the requirement for direct modification of Keap1.
Positive_regulation (activated) of Nrf2
13) Confidence 0.69 Published 2008 Journal Hepatology Section Abstract Doc Link 18785192 Disease Relevance 0.06 Pain Relevance 0.25
Nrf2 activation has been proposed to occur through the modification of cysteine residues within Keap1, the cytosolic repressor of Nrf2.
Positive_regulation (activation) of Nrf2
14) Confidence 0.69 Published 2008 Journal Hepatology Section Abstract Doc Link 18785192 Disease Relevance 0.18 Pain Relevance 0.26
Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity.
Positive_regulation (activates) of Nrf2 in Hepatocyte associated with toxicity and analgesic
15) Confidence 0.69 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Title Doc Link 16293230 Disease Relevance 0.17 Pain Relevance 0.16
Germ line deletion of the keap1 gene results in constitutive activation of Nrf2, but the pups unexpectedly died before weaning.
Positive_regulation (activation) of Nrf2 in Germ line
16) Confidence 0.69 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 16293230 Disease Relevance 0.15 Pain Relevance 0.05
These results demonstrate that chronic activation of Nrf2 confers animals with resistance to xenobiotics without affecting the morphological and physiological integrity of hepatocytes.
Positive_regulation (activation) of Nrf2 in hepatocytes
17) Confidence 0.69 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 16293230 Disease Relevance 0.16 Pain Relevance 0.10
Homozygous mice were viable and their livers displayed no apparent abnormalities, but nuclear accumulation of Nrf2 is elevated.
Positive_regulation (accumulation) of Nrf2 in livers associated with congenital anomalies
18) Confidence 0.69 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 16293230 Disease Relevance 0.17 Pain Relevance 0.08
To investigate how constitutive activation of Nrf2 influences the detoxification system in adult mice, we generated mice bearing a hepatocyte-specific disruption of the keap1 gene.
Spec (investigate) Positive_regulation (activation) of Nrf2 in hepatocyte
19) Confidence 0.69 Published 2006 Journal Biochem. Biophys. Res. Commun. Section Abstract Doc Link 16293230 Disease Relevance 0.16 Pain Relevance 0.06
All three chemicals induced Nrf2, but NF-kappaB binding activity was only increased after BSO treatment.
Positive_regulation (induced) of Nrf2
20) Confidence 0.66 Published 2010 Journal Biochem. Pharmacol. Section Abstract Doc Link 20416283 Disease Relevance 0.53 Pain Relevance 0.13

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