INT172479

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Context Info
Confidence 0.70
First Reported 2002
Last Reported 2010
Negated 0
Speculated 2
Reported most in Body
Documents 74
Total Number 76
Disease Relevance 35.22
Pain Relevance 0.79

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
A549 2
somatic cells 1
Hepa-1c1c7 1
bladder 1
internal 1
NFE2L2 (Homo sapiens)
Pain Link Frequency Relevance Heat
Inflammation 175 98.52 Very High Very High Very High
long-term potentiation 22 78.80 Quite High
Glutamate 68 71.08 Quite High
metalloproteinase 14 68.24 Quite High
Pain 16 60.96 Quite High
Osteoarthritis 6 60.48 Quite High
Paracetamol 37 55.84 Quite High
Central nervous system 22 43.72 Quite Low
antagonist 4 42.84 Quite Low
fibrosis 3 29.24 Quite Low
Disease Link Frequency Relevance Heat
Stress 673 99.96 Very High Very High Very High
Lung Cancer 1424 99.90 Very High Very High Very High
Cancer 2912 99.84 Very High Very High Very High
Nicotine Addiction 129 99.84 Very High Very High Very High
Non-small-cell Lung Cancer 600 99.58 Very High Very High Very High
Death 749 99.54 Very High Very High Very High
Apoptosis 754 99.20 Very High Very High Very High
Toxicity 565 99.08 Very High Very High Very High
INFLAMMATION 165 98.52 Very High Very High Very High
Breast Cancer 137 98.04 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Upon induction, Nrf2 is stabilized because of impaired Keap1-E3 ubiquitin ligase activity, which results in activation of the Nrf2 signaling pathway (Cullinan et al. 2004; Furukawa and Xiong 2005; Kobayashi et al. 2004; Sun et al. 2007; Zhang et al. 2004b).
Positive_regulation (activation) of Nrf2
1) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
M appeared to be toxic, and induction of Nrf2 was decreased (Figure 4A, lanes 7–9).
Positive_regulation (induction) of Nrf2
2) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.13 Pain Relevance 0
This paradox may be explained by the balance between the induction of the Nrf2 defensive response and the toxic outcome elicited by a particular compound.
Positive_regulation (induction) of Nrf2
3) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
Mechanistic studies presented here indicate that oridonin induced the Nrf2-dependent response primarily by enhancing the Nrf2 protein level.
Positive_regulation (enhancing) of Nrf2 protein
4) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.06 Pain Relevance 0.05
First, we determined activation of the Nrf2 pathway by oridonin in this cell line.
Spec (determined) Positive_regulation (activation) of Nrf2
5) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.19 Pain Relevance 0
Chemopreventive compounds are able to activate the Nrf2-dependent adaptive response and thus confer protection against subsequent toxic or carcinogenic damage (Jeong et al. 2006; Yates and Kensler 2007).
Positive_regulation (activate) of Nrf2
6) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
Next, we determined the oridonin dose range that induces Nrf2 protein in UROtsa cells.
Positive_regulation (induces) of Nrf2 protein
7) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.15 Pain Relevance 0
The increase in the Nrf2 protein level in response to oridonin is attributed mainly to the stabilization of Nrf2, with minor contribution from increased mRNA.
Positive_regulation (increase) of Nrf2 protein
8) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.07 Pain Relevance 0.05
In the present study, the effect of oridonin in inducing the Nrf2 protein level was assessed in two different cell lines, breast carcinoma MDA-MB-231 cells and immortalized but non-transformed bladder urothelium UROtsa cells.
Positive_regulation (inducing) of Nrf2 protein in bladder associated with breast cancer
9) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.62 Pain Relevance 0
The increase in the Nrf2 protein level in response to oridonin is attributed mainly to the stabilization of Nrf2, with minor contribution from increased mRNA.
Positive_regulation (stabilization) of Nrf2
10) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.07 Pain Relevance 0
UROtsa cells showed a narrower window of Nrf2 induction in response to different doses of oridonin.
Positive_regulation (induction) of Nrf2
11) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.63 Pain Relevance 0
Consistent with a decrease in ubiquitination of Nrf2 in response to oridonin, the half life of Nrf2 was increased from 10 min in the untreated condition to 16 min in response to oridonin treatment (Figure 3B, right panel).
Positive_regulation (increased) of Nrf2
12) Confidence 0.70 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.17 Pain Relevance 0
Real-time RT-PCR analysis of NRF2 and NRF2-dependent target genes revealed that the majority of the NRF2 target genes were upregulated in the cancer cells (Figure 4D).
Positive_regulation (upregulated) of NRF2 associated with cancer
13) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.04 Pain Relevance 0
To further demonstrate that NRF2 activation contributes to the increased expression of antioxidants, xenobiotic metabolism enzymes, and drug efflux pumps in cancer cells, we challenged A549 cells with siRNA targeting NRF2, and BEAS2B cells with KEAP1 siRNA.
Positive_regulation (activation) of NRF2 in A549 associated with cancer
14) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.71 Pain Relevance 0
Here, we report—to our knowledge for the first time—biallelic inactivation of KEAP1 in NSCLC, which we believe would result in constitutive activation of NRF2.
Positive_regulation (activation) of NRF2 associated with non-small-cell lung cancer
15) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.04 Pain Relevance 0
It is also possible that chronic oxidative stress, resulting from increased metabolic activity in cancer cells, is contributing to activation of NRF2.
Positive_regulation (activation) of NRF2 associated with stress and cancer
16) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.98 Pain Relevance 0
The identification of KEAP1 mutations in a subset of NSCLC samples and the association between loss of functional KEAP1 and increased NRF2 activity extends the emerging paradigm whereby increased expression of antioxidants, detoxification enzymes, and drug transporters favors malignant progression and renders tumors resistant to chemotherapy.
Positive_regulation (increased) of NRF2 associated with malignant neoplastic disease, cancer and non-small-cell lung cancer
17) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.11 Pain Relevance 0
Total NRF2 level was also higher in cancer cells, suggesting that there was increased stabilization of NRF2 in the absence of functional KEAP1.
Positive_regulation (stabilization) of NRF2 associated with cancer
18) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.92 Pain Relevance 0
In the absence of functional KEAP1 activity, cancer cells demonstrated an increased nuclear accumulation of NRF2 as well as an increase in total NRF2.
Positive_regulation (accumulation) of NRF2 associated with cancer
19) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 1.08 Pain Relevance 0
If future experiments verify that enhanced activation of NRF2 is a key cause of chemoresistance and poor prognosis, one could envision development of specific siRNA or small molecule inhibitors of NRF2 for treatment of patients with tumors resistant to chemotherapy.


Positive_regulation (activation) of NRF2 associated with cancer
20) Confidence 0.66 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.83 Pain Relevance 0

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