INT154816

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Context Info
Confidence 0.41
First Reported 2008
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 19
Total Number 23
Disease Relevance 11.38
Pain Relevance 1.84

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

cytosol (Sphk1) plasma membrane (Sphk1) nucleus (Sphk1)
DNA binding (Sphk1) kinase activity (Sphk1) cytoplasm (Sphk1)
Anatomy Link Frequency
PC-3 2
colon 1
Sphk1 (Mus musculus)
Pain Link Frequency Relevance Heat
Pain 4 99.28 Very High Very High Very High
Inflammation 90 99.20 Very High Very High Very High
IPN 1 99.04 Very High Very High Very High
cytokine 2 97.92 Very High Very High Very High
withdrawal 65 95.20 Very High Very High Very High
Central nervous system 1 90.92 High High
agonist 57 88.80 High High
intrathecal 2 88.80 High High
antagonist 36 88.24 High High
cINOD 1 85.68 High High
Disease Link Frequency Relevance Heat
Colon Cancer 3 99.30 Very High Very High Very High
Pain 2 99.28 Very High Very High Very High
INFLAMMATION 87 99.20 Very High Very High Very High
Inflammatory Pain 1 99.04 Very High Very High Very High
Colitis 3 98.90 Very High Very High Very High
Asthma 80 98.88 Very High Very High Very High
Targeted Disruption 22 98.24 Very High Very High Very High
Starvation 16 98.20 Very High Very High Very High
Adhesions 5 96.12 Very High Very High Very High
Metastasis 96 94.08 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Because an inhibition of SphK1 was observed during short-term androgen deprivation in vitro (Fig. 1D) and in vivo (Fig. 2B), we verified whether transfection of LNCaP cells with SphK1 might render these cells more resistant to androgen depletion.
Negative_regulation (inhibition) of SphK1
1) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.71 Pain Relevance 0
In PC-3 cells, a significant and lasting decrease in SphK1 activity was only observed under serum deprivation conditions (Fig. 1D, right panel). mirroring the impact on cell proliferation (Fig. 1C).
Negative_regulation (decrease) of SphK1 in PC-3
2) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.29 Pain Relevance 0
Similarly, the addition of dihydrotestosterone (DHT) to androgen-deprived LNCaP cells re-established cell proliferation, through an androgen receptor/PI3K/Akt dependent stimulation of SphK1, and inhibition of SphK1 could markedly impede the effects of DHT.
Negative_regulation (inhibition) of SphK1
3) Confidence 0.41 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2779655 Disease Relevance 0.35 Pain Relevance 0
Importantly, inhibition of the PI3K/Akt pathway—by negatively impacting SphK1 activity—could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors.
Negative_regulation (inhibitors) of SphK1
4) Confidence 0.41 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2779655 Disease Relevance 0.32 Pain Relevance 0
On the contrary, androgen deprivation did not alter the growth of PC-3 hormono-refractory (HR) cells whose growth was only altered by serum starvation (Fig. 1C).When compared to FBS conditions, androgen depletion in LNCaP induced a notable decrease in SphK1 activity within the first 24 h (Fig. 1D, left panel).
Negative_regulation (decrease) of SphK1 in PC-3 associated with starvation
5) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.24 Pain Relevance 0
Indeed, while wortmannin (WT) inhibited both the activation of Akt (Fig. 4B, top) and SphK1 (Fig. 4B, bottom) induced by DHT, the SphK1 inhibitor SKI-2 did not impact Akt phosphorylation (Fig. 4B, top).
Negative_regulation (inhibitor) of SphK1
6) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0 Pain Relevance 0.03
Importantly, inhibition of the PI3K/Akt pathway—by negatively impacting SphK1 activity—could prevent NE differentiation in both cell models, an event that could be mimicked by SphK1 inhibitors.
Negative_regulation (impacting) of SphK1
7) Confidence 0.41 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2779655 Disease Relevance 0.36 Pain Relevance 0
Later, a rebound in SphK1 activity was observed, which became significant beyond 4 days of treatment (Fig. 1D, left panel).
Negative_regulation (rebound) of SphK1
8) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.23 Pain Relevance 0
Supporting the critical role of SphK1 inhibition in the rapid effect of androgen depletion, its overexpression could impair the cell growth decrease.
Negative_regulation (inhibition) of SphK1
9) Confidence 0.41 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2779655 Disease Relevance 0.40 Pain Relevance 0
SphK1 activity was quantified as described previously [52], and determined in the presence of 50 µM sphingosine, 0.25% Triton X-100 and [?
Spec (determined) Negative_regulation (determined) of SphK1
10) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0 Pain Relevance 0
Based on our previous observations that SphK1 activity upon androgen deprivation was only transiently inhibited with a significant rebound within 4 days of incubation in CSS medium (Fig. 1D), we then analyzed the SphK1 activity up to 42 days during the NE transdifferentiation process.
Negative_regulation (inhibited) of SphK1
11) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.07 Pain Relevance 0
The efficacy of castration was associated with a significant decrease in SphK1 activity in tissue extracts (Fig. 2B, right panel).
Negative_regulation (decrease) of SphK1
12) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.82 Pain Relevance 0
Remarkably, under androgen deprivation conditions, a similar increase in cAMP intracellular levels was observed, which could not be blocked by pharmacological inhibition of SphK1 (Fig. 7D).
Negative_regulation (inhibition) of SphK1
13) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.15 Pain Relevance 0.11
Interestingly, the pharmacoligical inhibition of SphK1 did not have any effect on cAMP levels (Fig. 7B) whereas it did markedly inhibit NED (Fig. 7C).
Negative_regulation (inhibition) of SphK1
14) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.11 Pain Relevance 0.10
Moreover, both secretion of NSE (Fig. 6D, left panel) and CgA accumulation (Fig. 6D, right panel and Figure S1) were markedly diminished while Akt phosphorylation was unchanged hence suggesting that SphK1 inhibition can to a certain extent block the NE transdifferentiation.
Negative_regulation (inhibition) of SphK1
15) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0 Pain Relevance 0
In fact, similar to the PI3K inhibitors WT and LY294002 (Fig. 4C), the SphK1 inhibitors SKI-2 and F-12509a could impede DHT-induced cell proliferation, DNA synthesis as well as PSA secretion (Fig. 4D).
Negative_regulation (inhibitors) of SphK1
16) Confidence 0.41 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0 Pain Relevance 0.08
Pharmacological inhibition of sphingosine kinases (SPHK) decreased basal pain thresholds and SphK2 knock-out mice, but not SphK1 knock-out mice, had a significant decrease in withdrawal latency.
Negative_regulation (inhibition) of SPHK associated with targeted disruption, pain and withdrawal
17) Confidence 0.31 Published 2008 Journal J. Biol. Chem. Section Abstract Doc Link 18805787 Disease Relevance 0.79 Pain Relevance 0.48
The results that S1P aggravated antigen-induced airway inflammation might be consistent with the previous report that pharmacological inhibition of sphingosine kinase (SphK) attenuated airway inflammation in mouse experimental asthma [9].
Negative_regulation (inhibition) of sphingosine kinase associated with asthma and inflammation
18) Confidence 0.26 Published 2010 Journal The Open Respiratory Medicine Journal Section Body Doc Link PMC3024555 Disease Relevance 0.77 Pain Relevance 0.21
The results that S1P aggravated antigen-induced airway inflammation might be consistent with the previous report that pharmacological inhibition of sphingosine kinase (SphK) attenuated airway inflammation in mouse experimental asthma [9].
Negative_regulation (inhibition) of SphK associated with asthma and inflammation
19) Confidence 0.26 Published 2010 Journal The Open Respiratory Medicine Journal Section Body Doc Link PMC3024555 Disease Relevance 0.77 Pain Relevance 0.21
Indeed, inhalation of inhibitors for sphingosine kinase (SphK), which produces S1P directly from sphingosine, attenuated antigen-induced airway inflammation in mice [9].
Negative_regulation (inhibitors) of SphK associated with inflammation
20) Confidence 0.19 Published 2010 Journal The Open Respiratory Medicine Journal Section Body Doc Link PMC3024555 Disease Relevance 1.33 Pain Relevance 0.21

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