INT256913

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Context Info
Confidence 0.46
First Reported 2008
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 6
Total Number 41
Disease Relevance 35.30
Pain Relevance 0.10

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

nucleus (Hr) DNA binding (Hr)
Anatomy Link Frequency
MEF 6
cerebellar granule cells 1
Poly 1
hair follicle 1
brain 1
Hr (Mus musculus)
Pain Link Frequency Relevance Heat
Hippocampus 36 93.08 High High
midbrain 4 54.72 Quite High
ischemia 36 30.04 Quite Low
Pain 36 25.92 Quite Low
cytokine 4 25.32 Quite Low
Action potential 12 5.00 Very Low Very Low Very Low
tetrodotoxin 4 5.00 Very Low Very Low Very Low
IPN 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Apoptosis 2824 100.00 Very High Very High Very High
Papillomavirus Infection 14 100.00 Very High Very High Very High
Targeted Disruption 1080 99.86 Very High Very High Very High
Stress 360 99.48 Very High Very High Very High
Death 289 98.84 Very High Very High Very High
Sprains And Strains 37 97.40 Very High Very High Very High
Necrosis 144 94.92 High High
Huntington's Chorea 36 94.16 High High
Injury 72 91.16 High High
Urological Neuroanatomy 108 88.80 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In COS cells, the expression of Hr resulted in less cytochrome C release from mitochondria and in cerebellar granule cells, the decrease in membrane potential was greater in cultures from cerebellar granule cells from Hr knockout mice.
Gene_expression (expression) of Hr in cerebellar granule cells associated with targeted disruption
1) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 1.08 Pain Relevance 0
We suggest that the developmental changes in Hr expression explains, in part, why cell death occurs more commonly through apoptosis in the immature rat brain whereas cell death through necrosis is more commonly observed in the adult [41], [42].


Gene_expression (expression) of Hr in brain associated with necrosis, apoptosis and death
2) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.63 Pain Relevance 0
In a p53 reporter gene activity assay, Hr expressing and mock transfected cells displayed increases in luciferase activity after treatment with staurosporine and tunicamycin compared to non treated cells.
Gene_expression (expressing) of Hr
3) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.76 Pain Relevance 0
In cells expressing Hr, the levels of p53 were much lower.
Gene_expression (expressing) of Hr
4) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.84 Pain Relevance 0
Similarly, caspase-3 activity was approximately two-fold higher in mock transfected cells compared to cells expressing Hr after treatment with either chemical.
Gene_expression (expressing) of Hr
5) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.55 Pain Relevance 0
Finally, expression of Hr decreased levels of activated caspase 3 and Poly(ADP-ribose) polymerase-1 on Western blots (supplementary data figure S1).


Gene_expression (expression) of Hr in Poly
6) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.66 Pain Relevance 0
To determine if the early stages of the ER stress response was affected by Hr expression, levels of the protein chaperone GRP78 and the transcription factor CHOP were examined in COS cells treated with tunicamycin.
Gene_expression (expression) of Hr associated with stress
7) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 1.49 Pain Relevance 0
Similarly, levels of Bax, which is regulated by p53, were also lower in cell expressing Hr (figure 4).
Gene_expression (expressing) of Hr
8) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.73 Pain Relevance 0
A decrease in p53 dependent transcription, and in levels of Bax, which is regulated by p53 [30], was observed in COS cells expressing Hr.
Gene_expression (expressing) of Hr
9) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 1.09 Pain Relevance 0
In cells treated with tunicamycin, the number of cells displaying fragmented nuclei was approximately two-fold higher in mock transfected cells compared to cells expressing Hr.
Gene_expression (expressing) of Hr
10) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.50 Pain Relevance 0
Mock transfected cultures displayed approximately four-fold more cells with fragmented nuclei than cells expressing Hr after treatment with staurosporine (figure 1).
Gene_expression (expressing) of Hr
11) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.61 Pain Relevance 0
As expected, the expression of p53 protein increased in mock Hr transfected COS cells treated with either tunicamycin or staurosporine (figure 4).
Gene_expression (transfected) of Hr
12) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.94 Pain Relevance 0
Indeed, the percent increase in viability afforded by expressing Hr was significantly greater in wild type MEF compared to p53 knockout MEF after treatment with staurosporine and tunicamycin (figure 5).
Gene_expression (expressing) of Hr in MEF associated with targeted disruption
13) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.76 Pain Relevance 0
Although stress was observed as indicated by increased levels of both proteins, forced expression of Hr did not reduce the amount of stress.
Gene_expression (expression) of Hr associated with stress
14) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 1.45 Pain Relevance 0
Neither staurosporine nor tunicamycin increased the percentage of fragmented nuclei in wild type MEF expressing Hr.
Gene_expression (expressing) of Hr in MEF
15) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.66 Pain Relevance 0
To determine whether the effects of Hr are mediated through decreased expression and activity of p53, the effects of Hr on apoptosis were examined in mouse embryonic fibroblast (MEF) cell lines derived from p53 knock out and wild-type mice.
Gene_expression (expression) of Hr in MEF associated with targeted disruption and apoptosis
16) Confidence 0.40 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.74 Pain Relevance 0
In contrast, the responses of p53 knockout MEFs to staurosporine and tunicamycin were not attenuated by forced expression of Hr.
Gene_expression (expression) of Hr associated with targeted disruption
17) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.69 Pain Relevance 0
Finally, Hr expression did not attenuate apoptosis in mouse embryonic fibroblasts from p53 knockout mice but was effective in mouse embryonic fibroblasts from wild type mice.


Gene_expression (expression) of Hr in fibroblasts associated with targeted disruption and apoptosis
18) Confidence 0.36 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2944824 Disease Relevance 0.99 Pain Relevance 0
High levels of Hr protein expression were observed in the majority of cells at 48 hrs after transfection (figure 1).
Gene_expression (expression) of Hr protein
19) Confidence 0.36 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 1.17 Pain Relevance 0
One possibility is that Hr decreases levels of p53 by promoting p53 degradation through a proteosome dependent pathway. p53 has previously been shown to be deacetylated through formation of a complex with the E3 ligase MDM2[31], [32], [33], and histone deacetylates (HDAC), for example HDAC1[34], resulting in proteosomal degradation of p53 [35], or p53 export from nucleus[36].
Gene_expression (decreases) of Hr in nucleus
20) Confidence 0.35 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2944824 Disease Relevance 0.86 Pain Relevance 0

General Comments

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