INT138437

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Context Info
Confidence 0.65
First Reported 2006
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 23
Total Number 24
Disease Relevance 10.01
Pain Relevance 2.61

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
liver 3
plug 2
null cells 2
renal proximal tubule 1
PC-3 1
Sphk1 (Mus musculus)
Pain Link Frequency Relevance Heat
isoflurane 42 99.76 Very High Very High Very High
palliative 11 97.80 Very High Very High Very High
Inflammation 276 97.36 Very High Very High Very High
antagonist 44 94.84 High High
Paracetamol 3 92.72 High High
ischemia 6 92.36 High High
rheumatoid arthritis 260 89.60 High High
anesthesia 15 89.20 High High
Arthritis 256 82.64 Quite High
abdominal pain 4 76.88 Quite High
Disease Link Frequency Relevance Heat
Cancer 599 98.88 Very High Very High Very High
Recurrence 22 98.70 Very High Very High Very High
Injury 6 98.36 Very High Very High Very High
Asthma 42 98.28 Very High Very High Very High
INFLAMMATION 170 97.36 Very High Very High Very High
Disease 57 96.50 Very High Very High Very High
Reprotox - General 1 341 96.20 Very High Very High Very High
Carcinoma 10 94.72 High High
Cv Unclassified Under Development 6 92.36 High High
Severe Combined Immunodeficiency 55 92.24 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In order to determine whether the in vitro findings of the potential involvement of SphK1 in NE differentiation had any relevance to human disease, sections from a representative patient who underwent palliative transurethral resection for local recurrence under complete androgen blockade were immunostained for CgA and SphK1 expression (Fig. 8).
Gene_expression (expression) of SphK1 associated with disease, recurrence and palliative
1) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.34 Pain Relevance 0.13
The SphK1 activity of SphK1-overexpressing LNCaP (Fig. 3A, right panel) was increased to ?
Gene_expression (activity) of SphK1
2) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.54 Pain Relevance 0
SphK1 overexpression markedly inhibited the antiproliferative effect resulting from androgen removal.
Gene_expression (overexpression) of SphK1
3) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.55 Pain Relevance 0
As anticipated in PC-3 cells that are unaffected by CSS conditions, no significant SphK1 changes could be evidenced (Fig. 1C, D).


Gene_expression (changes) of SphK1 in PC-3
4) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.41 Pain Relevance 0
The SphK1 activity of SphK1-overexpressing LNCaP (Fig. 3A, right panel) was increased to ?
Gene_expression (activity) of SphK1
5) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.54 Pain Relevance 0
The instrumental role of SphK1 inhibition in reduced cell growth was confirmed by cell viability assays, which showed that LNCaP overexpressing SphK1 were markedly less sensitive to the effects of androgen depletion (Fig. 3B).
Gene_expression (overexpressing) of SphK1
6) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.36 Pain Relevance 0
These results emphasize other findings establishing that enforced expression of SphK1 displays a cytoprotective effect against various stimuli such as chemotherapeutics notably in prostate cancer cells [36].
Gene_expression (expression) of SphK1 associated with reprotox - general 1
7) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.48 Pain Relevance 0
In parallel, SphK1 protein expression was significantly increased (Fig. 6B, right panel).
Gene_expression (expression) of SphK1 protein
8) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.05 Pain Relevance 0
Concomitantly, SphK1 enforced expression was associated with a higher secretion of PSA in CSS-treated LNCaP cells reflecting its effects on cell proliferation (Fig. 3C).


Gene_expression (expression) of SphK1
9) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.28 Pain Relevance 0
Conversely, long-term removal of androgen support in LNCaP and C4-2B cells resulted in a progressive increase in SphK1 expression and activity throughout the progression to androgen-independence state, which was characterized by the acquisition of a neuroendocrine (NE)-like cell phenotype.
Gene_expression (expression) of SphK1
10) Confidence 0.65 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2779655 Disease Relevance 0.33 Pain Relevance 0
The observed SphK1 inhibition was not relying on de novo synthesis of ceramide (data not shown), which has been previously reported to accumulate following androgen ablation in LNCaP cells [48].
Gene_expression (inhibition) of SphK1
11) Confidence 0.65 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2779655 Disease Relevance 0.60 Pain Relevance 0
In order to test our hypothesis whether ceramide synthase inhibition by fumonisin B1 alters other sphingolipid-metabolizing enzymes, we investigated the changes in free sphingoid bases and sphingomyelin (SM) and activities of key enzymes for their metabolism, sphingomyelinase (SMase), serine palmitoyltransferase (SPT), and sphingosine kinase (SPHK) in mouse liver.
Gene_expression (metabolism) of SPHK in liver
12) Confidence 0.62 Published 2006 Journal Toxicol. Sci. Section Abstract Doc Link 16960033 Disease Relevance 0 Pain Relevance 0.07
In order to test our hypothesis whether ceramide synthase inhibition by fumonisin B1 alters other sphingolipid-metabolizing enzymes, we investigated the changes in free sphingoid bases and sphingomyelin (SM) and activities of key enzymes for their metabolism, sphingomyelinase (SMase), serine palmitoyltransferase (SPT), and sphingosine kinase (SPHK) in mouse liver.
Gene_expression (metabolism) of sphingosine kinase in liver
13) Confidence 0.62 Published 2006 Journal Toxicol. Sci. Section Abstract Doc Link 16960033 Disease Relevance 0 Pain Relevance 0.07
The expression and activities of SPT and SPHK1 in liver increased significantly following fumonisin B1 treatment.
Gene_expression (expression) of SPHK1 in liver
14) Confidence 0.62 Published 2006 Journal Toxicol. Sci. Section Abstract Doc Link 16960033 Disease Relevance 0 Pain Relevance 0.09
F9 cells overexpressing SphK1 exhibited elevated DNA synthesis, whereas other S1P-accumulating cells or SPL-null cells overexpressing SphK1 did not.
Gene_expression (overexpressing) of SphK1 in null cells
15) Confidence 0.41 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.41 Pain Relevance 0.16
F9 cells overexpressing SphK1 exhibited elevated DNA synthesis, whereas other S1P-accumulating cells or SPL-null cells overexpressing SphK1 did not.
Gene_expression (overexpressing) of SphK1 in null cells
16) Confidence 0.41 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.39 Pain Relevance 0.15
SK activity as well as SK1 mRNA expression increased in both cultured human proximal tubule cells (HK-2) and mouse kidneys after exposure to isoflurane.
Gene_expression (expression) of SK1 mRNA in tubule associated with isoflurane
17) Confidence 0.38 Published 2007 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 17898040 Disease Relevance 0.66 Pain Relevance 0.63
Small interfering RNAs (siRNA) directed against SphK decreased SphK1 protein and inhibited TNF-?
Gene_expression (protein) of SphK1
18) Confidence 0.36 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.34 Pain Relevance 0.24
S1P is produced by the activation (i.e., phosphorylation) of sphingosine (Sph) via its 2 isoforms of sphingosine kinase-1/2 (SphK-1/2) resulting in the production of the prosurvival S1P molecule with decreasing levels of the proapoptotic Sph molecule [35].
Gene_expression (/) of SphK-1
19) Confidence 0.36 Published 2009 Journal Mediators of Inflammation Section Body Doc Link PMC2842969 Disease Relevance 0.43 Pain Relevance 0.09
We sought to determine whether isoflurane stimulates sphingosine kinase (SK) activity and synthesis of sphingosine-1-phosphate (S1P) in renal proximal tubule cells to mediate renal protection via the S1P signaling pathway.
Gene_expression (synthesis) of sphingosine kinase in renal proximal tubule associated with isoflurane
20) Confidence 0.29 Published 2007 Journal Am. J. Physiol. Renal Physiol. Section Abstract Doc Link 17898040 Disease Relevance 0.65 Pain Relevance 0.56

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