INT146194

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Context Info
Confidence 0.42
First Reported 2005
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 21
Total Number 21
Disease Relevance 11.05
Pain Relevance 3.22

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

cell differentiation (Rhoa) mitochondrion (Rhoa) cell morphogenesis (Rhoa)
intracellular (Rhoa) GTPase activity (Rhoa) cytoplasm (Rhoa)
Anatomy Link Frequency
dendrite 1
neuronal 1
fibroblasts 1
Rhoa (Mus musculus)
Pain Link Frequency Relevance Heat
intrathecal 12 99.84 Very High Very High Very High
substance P 52 98.08 Very High Very High Very High
Demyelination 12 95.16 Very High Very High Very High
Inflammation 87 95.08 Very High Very High Very High
Neuropathic pain 24 92.56 High High
Spinal cord 14 91.96 High High
Inflammatory response 4 91.04 High High
Thermal hyperalgesia 5 89.92 High High
allodynia 6 87.04 High High
orphanin 4 84.20 Quite High
Disease Link Frequency Relevance Heat
Mevalonate Kinase Deficiency 348 99.84 Very High Very High Very High
Apoptosis 283 99.22 Very High Very High Very High
Disorder Of Lipid Metabolism 152 98.68 Very High Very High Very High
Stress 25 98.04 Very High Very High Very High
Demyelinating Disease 14 95.16 Very High Very High Very High
INFLAMMATION 103 95.08 Very High Very High Very High
Adhesions 38 94.88 High High
Atherosclerosis 187 94.08 High High
Death 81 93.48 High High
Neuropathic Pain 30 92.56 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This mevalonate-induced RhoA translocation was also blocked by intrathecal pretreatment with GGTI-2133, indicating that the RhoA translocation is triggered by RhoA geranylgeranylation.
Negative_regulation (blocked) of RhoA associated with intrathecal
1) Confidence 0.42 Published 2008 Journal Pain Section Abstract Doc Link 17764839 Disease Relevance 0.70 Pain Relevance 0.74
BoNT/C3 is a useful pharmacological tool to block this LPA1-mediated changes, since it shows a potent and long-lasting blockade of RhoA pathway, a major downstream of signaling[16].
Negative_regulation (blockade) of RhoA
2) Confidence 0.33 Published 2006 Journal Mol Pain Section Body Doc Link PMC1562366 Disease Relevance 1.16 Pain Relevance 1.44
Again, MKD cells were more sensitive to treatment with simvastatin, with markedly increased levels of active soluble RhoA and decreased levels of active membrane-bound RhoA already observed after incubation with low concentrations of simvastatin.
Negative_regulation (decreased) of RhoA associated with mevalonate kinase deficiency
3) Confidence 0.32 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.63 Pain Relevance 0
Incubation with simvastatin decreased the levels of membrane-bound RhoA in both control and MKD cells (Fig. 1b).
Negative_regulation (decreased) of RhoA associated with mevalonate kinase deficiency
4) Confidence 0.32 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.88 Pain Relevance 0
Inhibition of HMG-CoA reductase, however, resulted in a stronger decrease of membrane-bound (i.e., geranylgeranylated) RhoA in MKD cells than in control cells (Houten et al 2003b).
Negative_regulation (decrease) of RhoA associated with mevalonate kinase deficiency
5) Confidence 0.32 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.47 Pain Relevance 0
Incubation with GGTI led to a reduction in membrane-bound RhoA and Rac1 that was similar for both control and MKD cells (Fig. 2b, g) and, in parallel, an increase in the levels of soluble RhoA and Rac1 (Fig. 2c and 2h).
Negative_regulation (reduction) of RhoA associated with mevalonate kinase deficiency
6) Confidence 0.32 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.30 Pain Relevance 0
Indeed, in MKD fibroblasts, a low concentration of simvastatin already inhibits the pathway, resulting in a substantial reduction of membrane-bound RhoA.
Negative_regulation (reduction) of RhoA in fibroblasts associated with mevalonate kinase deficiency
7) Confidence 0.32 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.55 Pain Relevance 0
Incubation with simvastatin led to an increase of active soluble RhoA and a decrease of active membrane-bound RhoA in a concentration-dependent manner in both control and MKD cells.
Negative_regulation (decrease) of RhoA associated with mevalonate kinase deficiency
8) Confidence 0.32 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.65 Pain Relevance 0
Similar reversal was also observed in mice i.t. pretreated with 10 pg of C3-typed botulinum toxin (BoNT/C3), a selective inhibitor of ADP-ribosylation of RhoA (Table 1).
Negative_regulation (inhibitor) of RhoA
9) Confidence 0.30 Published 2006 Journal Mol Pain Section Body Doc Link PMC1562366 Disease Relevance 0.30 Pain Relevance 0.46
We have found that apoptotic effects of statins are driven through inhibition of the small G proteins Rac-1 and RhoA.
Negative_regulation (inhibition) of RhoA associated with apoptosis
10) Confidence 0.23 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597201 Disease Relevance 0.72 Pain Relevance 0
/Smad signaling can be attributed to RhoA/ROCK inhibition.
Negative_regulation (inhibition) of RhoA
11) Confidence 0.23 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597201 Disease Relevance 0.61 Pain Relevance 0
Recently it was shown that ibuprofen is able to suppress RhoA activity in neuronal cells through PPAR?
Negative_regulation (suppress) of RhoA in neuronal
12) Confidence 0.19 Published 2010 Journal Frontiers in Aging Neuroscience Section Body Doc Link PMC2893374 Disease Relevance 0.60 Pain Relevance 0.55
RhoA blockade increased Smad3 phosphorylation induced by TGF-?
Negative_regulation (blockade) of RhoA
13) Confidence 0.17 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597201 Disease Relevance 0.45 Pain Relevance 0
Pretreatment with Y-27632, an inhibitor of the downstream RhoA mediator ROCK, enhanced Smad-dependent transcription and Smad3 phosphorylation caused by TGF-?
Negative_regulation (inhibitor) of RhoA
14) Confidence 0.17 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597201 Disease Relevance 0.30 Pain Relevance 0
through its main signaling pathway, the Smad proteins, via inhibition of the RhoA/ROCK pathway (Figure 11).
Negative_regulation (inhibition) of RhoA
15) Confidence 0.17 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2597201 Disease Relevance 0.15 Pain Relevance 0
Furthermore, HDL inhibit thrombin-induced human endothelial TF expression through inhibition of RhoA and activation of PI3K but not Akt/eNOS (Viswambharan et al 2004).
Negative_regulation (inhibition) of RhoA associated with disorder of lipid metabolism
16) Confidence 0.16 Published 2005 Journal Vascular Health and Risk Management Section Body Doc Link PMC1993938 Disease Relevance 1.17 Pain Relevance 0
In the first report [12], it was shown that the anti-invasive effect of ZOL resulted from an inhibition of RhoA geranyl-geranylation.
Negative_regulation (inhibition) of RhoA
17) Confidence 0.16 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1434759 Disease Relevance 0.14 Pain Relevance 0
In contrast, RhoA is a negative regulator of dendrite outgrowth in various organisms and cell types [47], [48].
Negative_regulation (regulator) of RhoA in dendrite
18) Confidence 0.14 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2919383 Disease Relevance 0.16 Pain Relevance 0.03
To assess if inhibition of geranyl-geranylation by ZOL impairs the biological activity of RhoA GTPase, we studied the LPA-induced formation of stress fibers.
Negative_regulation (impairs) of RhoA associated with stress
19) Confidence 0.12 Published 2006 Journal BMC Cancer Section Abstract Doc Link PMC1434759 Disease Relevance 0.27 Pain Relevance 0
RhoA, Cdc42 and Rac1 can be activated when GTP-bound, and inactivated, when GDP-bound.
Negative_regulation (inactivated) of RhoA
20) Confidence 0.10 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2842301 Disease Relevance 0.83 Pain Relevance 0

General Comments

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