INT116763

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Context Info
Confidence 0.78
First Reported 2004
Last Reported 2010
Negated 3
Speculated 4
Reported most in Body
Documents 63
Total Number 94
Disease Relevance 54.53
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.

signal transduction (IKBKAP) nucleolus (IKBKAP) nucleus (IKBKAP)
protein complex assembly (IKBKAP) DNA binding (IKBKAP) cytoplasm (IKBKAP)
Anatomy Link Frequency
nervous tissues 2
fibroblasts 2
neural 2
neuronal 2
neural crest 1
IKBKAP (Homo sapiens)
Pain Link Frequency Relevance Heat
Potency 92 98.32 Very High Very High Very High
unmyelinated 7 84.56 Quite High
imagery 127 80.68 Quite High
Pain 101 72.40 Quite High
Hsan 8 71.00 Quite High
Peripheral nervous system 63 12.76 Low Low
gABA 3 5.00 Very Low Very Low Very Low
Visceral pain 3 5.00 Very Low Very Low Very Low
c fibre 3 5.00 Very Low Very Low Very Low
Clonidine 2 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Familial Dysautonomia 9832 100.00 Very High Very High Very High
Targeted Disruption 189 99.68 Very High Very High Very High
Rare Diseases 127 97.68 Very High Very High Very High
Disease 759 96.76 Very High Very High Very High
Toxicity 145 96.08 Very High Very High Very High
Neurological Disease 63 95.72 Very High Very High Very High
Rheumatoid Arthritis 63 94.76 High High
Apoptosis 155 91.04 High High
Spinal Muscular Atrophy 29 88.40 High High
Cognitive Disorder 203 87.92 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
For FD, several drugs, including kinetin and tocotrienol, increase the levels of wild-type IKAP mRNA and protein.
Gene_expression (levels) of IKAP mRNA associated with familial dysautonomia
1) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.52 Pain Relevance 0
The skipped isoform produced from the mutant gene is unable to produce normal IKAP protein, and the levels of normal IKAP mRNA in FD patients fail to provide sufficient amounts of IKAP protein.
Neg (unable) Gene_expression (produce) of IKAP protein associated with familial dysautonomia
2) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.87 Pain Relevance 0
Increasing the expression level of IKAP mRNA over a certain threshold leads to an increase in full-length IKAP protein levels.
Gene_expression (expression) of IKAP mRNA
3) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.63 Pain Relevance 0
As shown in Figure 1C, right side, the skipped IKAP isoform was expressed at different levels in the FD cell lines compared to the heterozygous cell line.
Gene_expression (expressed) of IKAP associated with familial dysautonomia
4) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.59 Pain Relevance 0
The control cell lines and the heterozygous cell line expressed the wild-type IKAP protein at the expected size of 150 kDa at similar levels (1.2 less IKAP protein in heterozygous cells).
Gene_expression (expressed) of IKAP protein
5) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.60 Pain Relevance 0
The mutation results in a tissue-specific splicing defect: Exon 20 is skipped, leading to reduced IKAP protein expression.
Gene_expression (expression) of IKAP protein
6) Confidence 0.78 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC3012102 Disease Relevance 0.72 Pain Relevance 0
In order to test whether expression of genes in addition to IKAP was altered as a result of PS treatment, we performed a human gene expression microarray analysis (Human Gene 1.0, Affymetrix) of cDNA samples from FDB cells treated with 100 µg/ml PS.
Spec (whether) Gene_expression (expression) of IKAP
7) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.23 Pain Relevance 0
Tissues from the brain and nervous system express primarily mutant IKAP mRNA (skipping of exon 20), while other tissues express both wild-type and mutant mRNA in different ratios [4], [9], [10].
Gene_expression (express) of IKAP mRNA in nervous system
8) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.65 Pain Relevance 0.07
The control cell lines and the heterozygous cell line expressed the wild-type IKAP protein at the expected size of 150 kDa at similar levels (1.2 less IKAP protein in heterozygous cells).
Gene_expression (expressed) of IKAP protein
9) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.59 Pain Relevance 0
In contrast, tocotrienol, a member of the vitamin E family that was reported to induce IKAP expression in FD cells [36], [37], [38], did not affect IKAP mRNA expression in our system (Figure 7B); this observation is similar to that of another publication [39].
Gene_expression (expression) of IKAP associated with familial dysautonomia
10) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.77 Pain Relevance 0
It should be noted that the antibody used in this western blot (from BD Bioscience) can detect only the wild-type IKAP protein.
Gene_expression (detect) of IKAP protein
11) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.26 Pain Relevance 0
In contrast, tocotrienol, a member of the vitamin E family that was reported to induce IKAP expression in FD cells [36], [37], [38], did not affect IKAP mRNA expression in our system (Figure 7B); this observation is similar to that of another publication [39].
Gene_expression (expression) of IKAP mRNA associated with familial dysautonomia
12) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3012102 Disease Relevance 0.78 Pain Relevance 0
In previous studies, one compound, kinetin (6-furfurylaminopurine) was found to correct IKBKAP splicing and increase IKAP/hELP1 production in FD cells [35].
Gene_expression (production) of IKAP/hELP1 associated with familial dysautonomia
13) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.56 Pain Relevance 0
Additionally, hOE-MSCs are an appropriate model for validating the potency of therapeutic agents such as kinetin, a cytokinin that has been shown to increase IKBKAP mRNA and protein expression in FD cell lines and in vivo models [20], [22], [35], [36] as well as in leukocytes of healthy carriers of the FD mutation [37].


Gene_expression (expression) of IKBKAP in leukocytes associated with familial dysautonomia and potency
14) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.90 Pain Relevance 0.05
Moreover, kinetin, by improving IKBKAP exon 20 recognition, restores IKBKAP transcript levels in FD hOE-MSCs similar to those observed in control cells (Figure 7G).
Gene_expression (levels) of IKBKAP associated with familial dysautonomia
15) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.24 Pain Relevance 0
In FD cells, the differential expression of IKBKAP transcripts was also correlated to a reduced expression of IKAP/hELP1 protein in FD, when compared to controls, as revealed by western blot analysis (Figure 2C).
Gene_expression (expression) of IKAP/hELP1 associated with familial dysautonomia
16) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.71 Pain Relevance 0
Using the hOE-MSCs model, we were also able to modulate the expression of IKBKAP WT and MU transcripts, by exposing the cells to different culture conditions to simulate variations in alternative splicing occurring during development and differentiation. hOE-MSCs form free floating spheres in approximately 7 days, when cultured with EGF and bFGF in serum-free medium.
Gene_expression (expression) of IKBKAP
17) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.40 Pain Relevance 0
Consistent results were observed for IKAP/hELP1 protein expression by western blot analysis, although a strong decrease of protein amount appeared after 24 h of wash out (Figure 7F).
Gene_expression (expression) of IKAP/hELP1
18) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.20 Pain Relevance 0
We also demonstrated that long time culture conditions and trypsin-EDTA mediated cell passages did not affect the IKBKAP gene expression pattern.
Gene_expression (expression) of IKBKAP
19) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.59 Pain Relevance 0
In one of the past studies, IKBKAP expression level can be downregulated by RNAi in control cells [10], where there is no production of MU transcripts.
Gene_expression (expression) of IKBKAP
20) Confidence 0.77 Published 2010 Journal PLoS ONE Section Body Doc Link PMC3004942 Disease Relevance 0.27 Pain Relevance 0

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