INT138671

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Context Info
Confidence 0.78
First Reported 2006
Last Reported 2010
Negated 1
Speculated 0
Reported most in Body
Documents 35
Total Number 35
Disease Relevance 7.34
Pain Relevance 6.03

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

cytosol (TPH2) small molecule metabolic process (TPH2) cellular nitrogen compound metabolic process (TPH2)
response to stress (TPH2)
Anatomy Link Frequency
hinge 3
brain 3
brainstem 3
lung 2
TPH2 (Homo sapiens)
TPH2 - R441H (1)
Pain Link Frequency Relevance Heat
Dopamine 9 100.00 Very High Very High Very High
fluoxetine 25 99.92 Very High Very High Very High
Raphe 58 99.68 Very High Very High Very High
medulla 36 99.52 Very High Very High Very High
Serotonin 109 99.48 Very High Very High Very High
Central nervous system 145 98.56 Very High Very High Very High
drug abuse 225 98.08 Very High Very High Very High
antidepressant 33 96.64 Very High Very High Very High
alcohol 57 96.20 Very High Very High Very High
depression 212 95.00 High High
Disease Link Frequency Relevance Heat
Small Cell Lung Carcinoma 28 99.60 Very High Very High Very High
Schizophrenia 204 99.20 Very High Very High Very High
Suicidal Behaviour 420 98.64 Very High Very High Very High
Disease 178 98.64 Very High Very High Very High
Pheochromocytoma 28 98.64 Very High Very High Very High
Drug Dependence 226 98.08 Very High Very High Very High
Depression 215 95.00 High High
Anxiety Disorder 94 94.40 High High
Genetic Predisposition To Disease 29 92.16 High High
Hypersensitivity 8 89.32 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Therefore, our data indicate a major loss of TPH2A 1234 enzymatic activity by RNA editing and support the recently reported 80% reduction of 5-HT synthesis in PC12 cells expressing the TPH2-R441H mutant [29].
Gene_expression (expressing) of TPH2-R441H (R441H)
1) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0 Pain Relevance 0.04
Instead of TPH2b 1234 we analyzed a TPH2b 234 cDNA, which we also detected in our samples (Figure 1A, Table 1), but lacks nonsense editing at position 1 (c.385C>T; p.Q129X) and enables the expression of a full-length TPH2B 234 protein.
Gene_expression (expression) of TPH2B
2) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.15 Pain Relevance 0.12
To determine 5-HT levels in stable TPH2-expressing PC12 cell lines, 1.7 million cells were homogenized in 100 µL buffer containing 5 mM sodium metabisulfite and 300 mM perchloric acid (Sigma-Aldrich).
Gene_expression (expressing) of TPH2
3) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.12 Pain Relevance 0.14
Moreover, TPH2b transcripts are also readily detectable in rat brain and human small cell lung carcinoma SHP77 cells, which express TPH2 (Figure 1D) together with other neuroendocrine markers.
Gene_expression (express) of TPH2 in lung associated with small cell lung carcinoma
4) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.10 Pain Relevance 0.04
To address this question, we stably expressed TPH2a and TPH2b and their edited isoforms in rat pheochromocytoma PC12 cells and performed kinetic studies with the cellular lysates (Figure 3A–D).
Gene_expression (expressed) of TPH2b associated with pheochromocytoma
5) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.17 Pain Relevance 0.05
In conclusion, our results underscore that human CNS 5-HT biosynthesis is a highly regulated process, which is based on the expression of a wide variety of functional TPH2 proteins with different properties.
Gene_expression (expression) of TPH2 associated with central nervous system
6) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.14 Pain Relevance 0.17
To address this question, we stably expressed TPH2a and TPH2b and their edited isoforms in rat pheochromocytoma PC12 cells and performed kinetic studies with the cellular lysates (Figure 3A–D).
Gene_expression (expressed) of TPH2a associated with pheochromocytoma
7) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.17 Pain Relevance 0.03
Cell pellets were boiled in 100 µL SDS loading buffer for 5-HT normalization to the TPH2 protein expression levels by immunoblotting.


Gene_expression (expression) of TPH2
8) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.39 Pain Relevance 0.09
However, TPH2B 234 activity, which was still consistently higher than for TPH2A, can be totally abolished by RNA editing at position 1 (c.385C>T; p.Q129X), resulting in a premature stop codon upstream of the catalytic domain [39] and the expression of an inactive, truncated TPH2B 1 protein.
Gene_expression (expression) of TPH2B
9) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0 Pain Relevance 0.10
Thus, the known 5-HT hypofunction in psychiatric disorders may result at least in part from the expression of the low active TPH2A 1234 protein in these individuals.
Gene_expression (expression) of TPH2A
10) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.54 Pain Relevance 0.20
The regulation of TPH2 expression reveals an unprecedented mechanism of mutually exclusive editing of the alternatively spliced isoforms TPH2a and TPH2b.
Gene_expression (expression) of TPH2
11) Confidence 0.78 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.65 Pain Relevance 0.09
Effect of repeated treatment with fluoxetine on tryptophan hydroxylase-2 gene expression in the rat brainstem.
Gene_expression (expression) of tryptophan hydroxylase-2 in brainstem associated with medulla and fluoxetine
12) Confidence 0.77 Published 2006 Journal Pharmacol. Biochem. Behav. Section Title Doc Link 16982082 Disease Relevance 0.26 Pain Relevance 0.59
Mol Psychiatry 2004; 9:879-889] may be related to the drug effect on the TPH2 gene expression.
Gene_expression (expression) of TPH2 gene
13) Confidence 0.77 Published 2006 Journal Pharmacol. Biochem. Behav. Section Abstract Doc Link 16982082 Disease Relevance 0.07 Pain Relevance 0.54
The expression of the four TPH2 variants in PC12 cells revealed equal 5-HT contents for TPH2A and TPH2B, and, unexpectedly, also for TPH2B 234, for which we had expected lower activity (Figure 3E).
Gene_expression (expression) of TPH2
14) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0 Pain Relevance 0.14
As brain 5-HT biosynthesis is regulated by TPH2 [6], [26], and TPH2 SNPs increase the risk for psychiatric disorders [27], [28], [29], we decided to further analyze the polymorphic variability of the human TPH2 gene and focused on its coding region.
Gene_expression (increase) of TPH2 in brain
15) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0.12 Pain Relevance 0.10
Interestingly, TPH2B presented the highest Vmax, which was twice as high as for TPH2A and well in accordance with the prediction that the GK insertion into the hinge region allows easier access of the substrates to the catalytic core.
Gene_expression (presented) of TPH2B in hinge
16) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0 Pain Relevance 0.08
Interestingly, TPH2B presented the highest Vmax, which was twice as high as for TPH2A and well in accordance with the prediction that the GK insertion into the hinge region allows easier access of the substrates to the catalytic core.
Gene_expression (high) of TPH2A in hinge
17) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0 Pain Relevance 0.07
Here we show that TPH2 exists in two alternatively spliced variants in the coding region, denoted TPH2a and TPH2b.
Gene_expression (denoted) of TPH2a
18) Confidence 0.68 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2813293 Disease Relevance 0.37 Pain Relevance 0.16
PC12 cells have been used to directly assess 5-HT synthesis of recombinant TPH2 mutants [29].
Gene_expression (synthesis) of TPH2
19) Confidence 0.68 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2813293 Disease Relevance 0 Pain Relevance 0.14
Here we show that TPH2 exists in two alternatively spliced variants in the coding region, denoted TPH2a and TPH2b.
Gene_expression (denoted) of TPH2b
20) Confidence 0.68 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2813293 Disease Relevance 0.37 Pain Relevance 0.16

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