INT186268

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Context Info
Confidence 0.50
First Reported 2005
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 13
Total Number 15
Disease Relevance 8.00
Pain Relevance 1.32

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

oxidoreductase activity (Tdo2)
Anatomy Link Frequency
plasma 3
liver 3
brain 1
granule cells 1
T cell 1
Tdo2 (Mus musculus)
Pain Link Frequency Relevance Heat
Inflammation 53 99.98 Very High Very High Very High
Serotonin 116 99.30 Very High Very High Very High
Inflammatory response 8 95.88 Very High Very High Very High
depression 88 86.84 High High
dexamethasone 6 86.76 High High
Eae 66 82.72 Quite High
Hippocampus 140 77.92 Quite High
cytokine 113 74.60 Quite High
nMDA receptor antagonist 6 73.56 Quite High
Glutamate 2 71.36 Quite High
Disease Link Frequency Relevance Heat
INFLAMMATION 61 99.98 Very High Very High Very High
Stress 492 99.96 Very High Very High Very High
Cold Sores 214 99.00 Very High Very High Very High
Infection 263 98.24 Very High Very High Very High
Disease 36 95.92 Very High Very High Very High
Bacterial Respiratory Disease 30 95.88 Very High Very High Very High
Anxiety Disorder 186 95.20 Very High Very High Very High
Neurodegenerative Disease 134 93.52 High High
Affective Disorder 14 92.16 High High
Congenital Anomalies 14 91.44 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
We then examined whether levels of the major Trp metabolites kynurenine (Kyn) and kynurenic acid (KYNA) were reduced by tdo deletion, on the basis that the marked elevation of Trp in Tdo-/- mice suggested the insufficient compensatory conversion of Trp to formylkynurenine by IDO.
Positive_regulation (elevation) of Tdo
1) Confidence 0.50 Published 2009 Journal Mol Brain Section Body Doc Link PMC2673217 Disease Relevance 0.08 Pain Relevance 0.03
We concluded that anti-TDO antibody was specifically reactive for TDO protein.
Positive_regulation (reactive) of TDO
2) Confidence 0.50 Published 2010 Journal Mol Brain Section Body Doc Link PMC2945337 Disease Relevance 0.08 Pain Relevance 0.03
Results showed that brain levels of Trp and 5-HT [2] were markedly elevated in Tdo-/- mice (Figure 3).
Positive_regulation (elevated) of Tdo in brain
3) Confidence 0.44 Published 2009 Journal Mol Brain Section Body Doc Link PMC2673217 Disease Relevance 1.44 Pain Relevance 0.26
Usefulness of TDO as a maturation marker of the dentate granule cells
Positive_regulation (Usefulness) of TDO in granule cells
4) Confidence 0.44 Published 2010 Journal Mol Brain Section Body Doc Link PMC2945337 Disease Relevance 0.11 Pain Relevance 0.11
Measurement of the three Trp catabolites in plasma by HPLC showed much higher levels of 5-HIAA, the catabolic product of Trp via the serotonin (5-HT) pathway (Figure 1A(b)), in Tdo-/- than Tdo+/+ mice (Figure 2C), as well as increases in indoleacetic acid (IAA) and indolelactic acid (ILA) (Figure 2D and 2E), products of Trp via the transamination pathway (Figure 1A(c)).
Positive_regulation (increases) of Tdo in plasma associated with serotonin
5) Confidence 0.41 Published 2009 Journal Mol Brain Section Body Doc Link PMC2673217 Disease Relevance 0.14 Pain Relevance 0.05
These mice had markedly increased plasma levels of Trp, 5-HIAA, ILA and IAA in the presence of IDO, demonstrating that the accumulation of Trp and acceleration of serotonergic and transamination pathways are largely dependent on TDO (Figure 1 and 2).
Positive_regulation (accumulation) of TDO in plasma
6) Confidence 0.41 Published 2009 Journal Mol Brain Section Body Doc Link PMC2673217 Disease Relevance 0.26 Pain Relevance 0.06
Indeed, stresses such as forced running, immobilization and exposure to cold increase rat liver TDO activity [43].
Positive_regulation (increase) of TDO in liver associated with stress
7) Confidence 0.41 Published 2009 Journal Mol Brain Section Body Doc Link PMC2673217 Disease Relevance 0.74 Pain Relevance 0.07
These mice had markedly increased plasma levels of Trp, 5-HIAA, ILA and IAA in the presence of IDO, demonstrating that the accumulation of Trp and acceleration of serotonergic and transamination pathways are largely dependent on TDO (Figure 1 and 2).
Positive_regulation (dependent) of TDO in plasma
8) Confidence 0.41 Published 2009 Journal Mol Brain Section Body Doc Link PMC2673217 Disease Relevance 0.25 Pain Relevance 0.06
Here, we investigated whether psychological stress (combined acoustic and restraint stress) activates the tryptophan (Trp) catabolizing enzyme indoleamine 2,3-dioxygenase 1(IDO1) and thereby alters the immune homeostasis and behavior in mice.
Spec (whether) Positive_regulation (activates) of tryptophan associated with stress
9) Confidence 0.33 Published 2010 Journal PLoS ONE Section Abstract Doc Link PMC2911374 Disease Relevance 0.70 Pain Relevance 0.09
Under basal conditions in mammals, Trp catabolism is mediated by tryptophan dioxygenase (TDO) activation - mainly in the liver - which is controlled by GCs [22], [27].
Positive_regulation (activation) of TDO in liver
10) Confidence 0.33 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2911374 Disease Relevance 0.75 Pain Relevance 0.11
Under basal conditions in mammals, Trp catabolism is mediated by tryptophan dioxygenase (TDO) activation - mainly in the liver - which is controlled by GCs [22], [27].
Positive_regulation (activation) of tryptophan dioxygenase in liver
11) Confidence 0.33 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2911374 Disease Relevance 0.76 Pain Relevance 0.11
It was demonstrated that increased tryptophan depletion via the IDO1 pathway increases the generation of kynurenines (see Fig. 1) which inhibit T cell responses and cause the development of dendritic cells with tolerogenic properties [22], [27].
Positive_regulation (increased) of tryptophan in T cell
12) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2911374 Disease Relevance 0.37 Pain Relevance 0.13
Surprisingly, GCs which primarily activate the TDO-driven Trp catabolism [22], [27] don't have the leading role for Trp depletion or for the loss of the antibacterial defense in our model of repeated stress.
Positive_regulation (activate) of TDO associated with stress and bacterial respiratory disease
13) Confidence 0.31 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2911374 Disease Relevance 0.79 Pain Relevance 0.09
This study highlights a new stress-inducible pathway which adds up to the neuroendocrine circuits known to suppress immune functions: (1) acute stress-induced low-grade inflammation induces transient IDO1-mediated tryptophan-catabolism and (2) prolonged Trp shortage due to expanded stressful episodes as well as the formation of kynurenines are immunosuppressive and simultaneously may induce mood alterations.


Positive_regulation (induces) of tryptophan associated with stress and inflammation
14) Confidence 0.29 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2911374 Disease Relevance 0.77 Pain Relevance 0.13
in inhibition of HSV replication has now been shown to be mediated by activation of a tryptophan-depleting enzyme [389].
Positive_regulation (activation) of tryptophan-depleting enzyme associated with cold sores
15) Confidence 0.01 Published 2005 Journal Virol J Section Body Doc Link PMC1215526 Disease Relevance 0.79 Pain Relevance 0

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