INT101818

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Context Info
Confidence 0.78
First Reported 2002
Last Reported 2010
Negated 1
Speculated 1
Reported most in Body
Documents 48
Total Number 49
Disease Relevance 23.80
Pain Relevance 0.66

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
nucleus 4
A549 2
internal 1
fibroblast 1
epithelial cells 1
NFE2L2 (Homo sapiens)
Pain Link Frequency Relevance Heat
Glutamate 46 98.92 Very High Very High Very High
Inflammation 90 95.56 Very High Very High Very High
metalloproteinase 3 80.04 Quite High
cINOD 14 69.28 Quite High
Paracetamol 14 66.00 Quite High
Ventral tegmentum 9 35.60 Quite Low
midbrain 2 33.36 Quite Low
palliative 20 27.20 Quite Low
psoriasis 22 5.00 Very Low Very Low Very Low
Substantia nigra 12 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Apoptosis 349 100.00 Very High Very High Very High
Toxicity 226 100.00 Very High Very High Very High
Repression 26 100.00 Very High Very High Very High
Cancer 2230 99.84 Very High Very High Very High
Targeted Disruption 27 99.84 Very High Very High Very High
Wound Healing 15 99.68 Very High Very High Very High
Lung Cancer 1108 98.56 Very High Very High Very High
Shock 46 98.12 Very High Very High Very High
Stress 430 97.24 Very High Very High Very High
INFLAMMATION 86 95.56 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Inhibition of Nrf2 expression in UROtsa cells reverted the MTT curve [i.e., oridonin lost its protection against As(III) toxicity] and aggravated As(III)-induced cell death (Figure 4D, center panel).
Gene_expression (expression) of Nrf2 associated with toxicity and death
1) Confidence 0.78 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.93 Pain Relevance 0
Immunoblot analysis confirmed the effectiveness of Nrf2-siRNA in reducing Nrf2 expression (Figure 4D, center panel).
Gene_expression (expression) of Nrf2
2) Confidence 0.78 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.79 Pain Relevance 0
Next, we measured mRNA expression of Nrf2 and its target genes, NQO1 and HO-1, in response to oridonin using real-time RT-PCR.
Gene_expression (expression) of Nrf2
3) Confidence 0.78 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.19 Pain Relevance 0
These mice express lower basal levels of the Nrf2 target genes such as NQO1, GST, GCS, UDP-glucuronosyltransferase, glutathione peroxidase-2, and HO-1 (Chan and Kwong 2000; Cho et al. 2002; Hayes et al. 2000; Kwak et al. 2001; McMahon et al. 2001).
Gene_expression (express) of Nrf2
4) Confidence 0.78 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.74 Pain Relevance 0.07
Consistent with this idea, over-expression of Nrf2 increased GCLC reporter gene expression and over-expression of KIAA0132 inhibited GCLC reporter gene activity as well as inhibited indomethacin-induced increases in the expression of GCLC.
Gene_expression (over-expression) of Nrf2
5) Confidence 0.74 Published 2002 Journal Free Radic. Biol. Med. Section Abstract Doc Link 11909699 Disease Relevance 0 Pain Relevance 0.12
Transfection of NRF2 siRNA in cancer cells decreased the NRF2 message by 80% and simultaneously downregulated the expression of NRF2 target genes (Figure 6B).
Gene_expression (expression) of NRF2 associated with cancer
6) Confidence 0.74 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.42 Pain Relevance 0
Transfection of NRF2 siRNA in cancer cells decreased the NRF2 message by 80% and simultaneously downregulated the expression of NRF2 target genes (Figure 6B).
Gene_expression (Transfection) of NRF2 associated with cancer
7) Confidence 0.74 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.53 Pain Relevance 0
Critically, the enhanced expression of various antioxidants and detoxification genes was verified to be NRF2-dependent, because siRNA targeted against NRF2 transcript attenuated the expression of these NRF2-dependent genes in A549 cells.
Gene_expression (expression) of NRF2 in A549
8) Confidence 0.74 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.75 Pain Relevance 0
Conversely, inhibition of KEAP1 expression by siRNA induced the expression of NRF2-driven genes in BEAS2B cells (Figure 6C).


Gene_expression (expression) of NRF2
9) Confidence 0.74 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.42 Pain Relevance 0
Expression analysis of NRF2-dependent genes revealed upregulation of antioxidant genes, detoxification enzymes, and drug efflux pumps in the cancer cells.
Gene_expression (Expression) of NRF2 associated with cancer
10) Confidence 0.74 Published 2006 Journal PLoS Medicine Section Body Doc Link PMC1584412 Disease Relevance 0.96 Pain Relevance 0
We purchased the antibodies for Nrf2, Keap1, and ?
Gene_expression (antibodies) of Nrf2
11) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
Taken together, these results indicate that oridonin activates the Nrf2 pathway by inhibiting ubiquitination and degradation of Nrf2, leading to an increase in Nrf2 protein level and activation of the Nrf2-dependent response.


Gene_expression (level) of Nrf2 protein
12) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.16 Pain Relevance 0
Compared with MDA-MB-231 cells (Figure 2B, lanes 2–7), UROtsa cells had a narrow range of Nrf2 induction, from 1.4 to 14?
Gene_expression (induction) of Nrf2 in MDA-MB-231
13) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.14 Pain Relevance 0
This decrease in Nrf2 protein level in response to high doses of oridonin is not due solely to cell toxicity because Keap1 or ?
Gene_expression (level) of Nrf2 protein associated with toxicity
14) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.63 Pain Relevance 0
Taken together, these results indicate that oridonin activates the Nrf2 pathway by inhibiting ubiquitination and degradation of Nrf2, leading to an increase in Nrf2 protein level and activation of the Nrf2-dependent response.


Gene_expression (level) of Nrf2
15) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.17 Pain Relevance 0
For detection of the ubiquitinated Nrf2 in vivo, cells were transfected with expression vectors for hemagglutinin (HA)-ubiquitin, Keap1, and Gal4-Neh2 (the N-terminal domain of Nrf2 containing the ubiquitin conjugating sites).
Gene_expression (detection) of Nrf2
16) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
In addition to GCS, which modulates intracellular glutathione levels, other Nrf2 downstream genes, including GST, UDP-glucuronosyl transferase, and multidrug resistance proteins, also contribute to the Nrf2-mediated protection against arsenic toxicity (Hayashi et al. 2003; Kobayashi and Yamamoto 2006; Maher et al. 2005; Vernhet et al. 2001; Xu et al. 2005; Zhang 2006).
Gene_expression (proteins) of Nrf2 associated with toxicity
17) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.35 Pain Relevance 0
Oridonin blocked Nrf2 ubiquitination and enhanced Keap1 ubiquitination
Gene_expression (ubiquitination) of Nrf2
18) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0 Pain Relevance 0
M, Nrf2 protein levels decreased in a dose-dependent manner, whereas the expression of Keap1 and ?
Gene_expression (levels) of Nrf2 protein
19) Confidence 0.67 Published 2008 Journal Environ Health Perspect Section Body Doc Link PMC2535615 Disease Relevance 0.23 Pain Relevance 0
The concerted higher expression of Nqo1, Nrf2 and other anti-oxidant genes in CA1, in comparison to CA3, is further evidence for the presence of high OS in neurons of this vulnerable region under basal conditions.
Gene_expression (expression) of Nrf2 in neurons associated with stress
20) Confidence 0.67 Published 2010 Journal Frontiers in Aging Neuroscience Section Body Doc Link PMC2874397 Disease Relevance 0.51 Pain Relevance 0

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