INT146197

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Context Info
Confidence 0.68
First Reported 2005
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 60
Total Number 60
Disease Relevance 34.12
Pain Relevance 12.02

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
nerve 3
smooth muscle 2
spinal cord 2
spinal 2
brain 1
Rhoa (Mus musculus)
Pain Link Frequency Relevance Heat
Spinal cord 93 99.82 Very High Very High Very High
c fibre 123 99.50 Very High Very High Very High
intrathecal 40 99.50 Very High Very High Very High
Dorsal horn 31 99.40 Very High Very High Very High
Pain 97 99.22 Very High Very High Very High
fibrosis 35 99.12 Very High Very High Very High
substance P 167 98.98 Very High Very High Very High
metalloproteinase 19 98.68 Very High Very High Very High
Neuropathic pain 127 97.84 Very High Very High Very High
Demyelination 64 97.64 Very High Very High Very High
Disease Link Frequency Relevance Heat
Spinal Cord Injury 32 99.96 Very High Very High Very High
Nervous System Injury 133 99.82 Very High Very High Very High
Mevalonate Kinase Deficiency 1276 99.48 Very High Very High Very High
Respiratory Syncytial Virus 3 99.48 Very High Very High Very High
Infection 30 99.44 Very High Very High Very High
Asthma 80 99.32 Very High Very High Very High
Pain 97 99.22 Very High Very High Very High
Nociception 124 99.20 Very High Very High Very High
Death 57 99.16 Very High Very High Very High
Adhesions 51 99.14 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Intrathecal injection of mevalonate increased the amount of geranylgeranylated RhoA in the spinal cord, which was completely blocked by intrathecal pretreatment with GGTI-2133.
Positive_regulation (increased) of RhoA in spinal cord associated with spinal cord and intrathecal
1) Confidence 0.68 Published 2008 Journal Pain Section Abstract Doc Link 17764839 Disease Relevance 0.69 Pain Relevance 0.81
Collectively, these findings suggest that a long-lasting activation of PKC and RhoA/Rho kinase pathways in the spinal cord may be responsible for the development of thermal hyperalgesia induced by nerve ligation in mice.
Positive_regulation (activation) of RhoA in nerve associated with thermal hyperalgesia and spinal cord
2) Confidence 0.67 Published 2007 Journal Nihon Shinkei Seishin Yakurigaku Zasshi Section Abstract Doc Link 17879593 Disease Relevance 0.49 Pain Relevance 0.81
Indeed, the current study also demonstrated a marked increase in the expression and activation of RhoA protein in BSMs of the AHR mice (Fig. 4 and 5).
Positive_regulation (activation) of RhoA protein
3) Confidence 0.60 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.13 Pain Relevance 0
If RhoA proteins are activated by receptors other than muscarinic receptor, it might account for the 'non-specific' AHR, which is a common feature of allergic asthmatics.
Positive_regulation (activated) of RhoA associated with hypersensitivity and occupational lung diseases
4) Confidence 0.60 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.66 Pain Relevance 0.18
Upregulation of RhoA protein in BSMs of OA-challenged mice
Positive_regulation (Upregulation) of RhoA protein
5) Confidence 0.60 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0 Pain Relevance 0
An upregulation of RhoA/Rho-kinase associated with the augmented smooth muscle contractility has also been reported in rat myomertium during pregnancy [42,43], arterial smooth muscle of spontaneously hypertensive rats [12], coronary vasospasm in pigs [16], dog femoral artery in heart failure [44], and BSMs in rat experimental asthma [21].
Positive_regulation (upregulation) of RhoA in smooth muscle associated with asthma, hypertension, coronary vasospasm and myocardial infarction
6) Confidence 0.60 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.61 Pain Relevance 0.11
It is thus likely that ACh stimulation activates the upregulated RhoA (Fig. 5), resulting in a greater phosphorylation of MLC (Fig. 6) and contraction of BSMs in AHR mice.
Positive_regulation (upregulated) of RhoA
7) Confidence 0.60 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.43 Pain Relevance 0.19
These observations are in a good contrast with the previous findings that the nerve injury-induced activation of LPA1 receptor and RhoA causes functional changes in myelinated A-fibers, such as demyelination and up-regulation of Ca2+ channel ?
Positive_regulation (activation) of RhoA in nerve associated with demyelination and nervous system injury
8) Confidence 0.55 Published 2006 Journal Mol Pain Section Body Doc Link PMC1562366 Disease Relevance 1.17 Pain Relevance 0.98
To confirm that the observed effect of simvastatin on RhoA and Rac1 activation was due to a shortage of GGPP, we studied the effect of GGTI, an inhibitor of geranylgeranyl transferase, on localization and activation of RhoA and Rac1 and found that GGTI had a similar effect as simvastatin.
Positive_regulation (activation) of RhoA
9) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.28 Pain Relevance 0
The increase in total cellular levels of active RhoA and Rac1 due to simvastatin appears primarily, if not solely, caused by activation of soluble RhoA and Rac1 and not membrane-bound RhoA and Rac1.
Positive_regulation (increase) of RhoA
10) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.11 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).
Positive_regulation (increase) of RhoA associated with mevalonate kinase deficiency
11) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.30 Pain Relevance 0
The relative increase in active RhoA was larger than the relative increase in active Rac1 (Fig. 1e, j).


Positive_regulation (increase) of RhoA
12) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.19 Pain Relevance 0
Because small GTPases depend on isoprenylation for their proper signalling function, we studied the effect of MK deficiency on isoprenylation (i.e., geranylgeranylation) and activation of the two small GTPases, RhoA and Rac1.
Positive_regulation (activation) of RhoA
13) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.51 Pain Relevance 0.04
Although the relative increase of soluble RhoA was higher in control cells after simvastatin treatment, levels of soluble RhoA were higher in MKD cells, which can be explained by the fact that untreated MKD cells already have higher levels of soluble RhoA.
Positive_regulation (increase) of RhoA associated with mevalonate kinase deficiency
14) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 0.89 Pain Relevance 0
In summary, we showed that protein isoprenylation in MKD cells is more sensitive to inhibition by simvastatin than in control cells, resulting in an increased, ectopic activation of soluble RhoA and Rac1 in MKD cells.
Positive_regulation (activation) of RhoA associated with mevalonate kinase deficiency
15) Confidence 0.51 Published 2010 Journal J Inherit Metab Dis Section Body Doc Link PMC2946549 Disease Relevance 1.09 Pain Relevance 0.08
This mevalonate-induced RhoA translocation was also blocked by intrathecal pretreatment with GGTI-2133, indicating that the RhoA translocation is triggered by RhoA geranylgeranylation.
Positive_regulation (mevalonate-induced) of RhoA associated with intrathecal
16) Confidence 0.49 Published 2008 Journal Pain Section Abstract Doc Link 17764839 Disease Relevance 0.70 Pain Relevance 0.74
Our present results suggest that mevalonate sensitizes the spinal nociceptive transmission, which is mediated by the activation of ROCK following the RhoA geranylgeranylation.
Positive_regulation (activation) of RhoA in spinal associated with nociception
17) Confidence 0.49 Published 2008 Journal Pain Section Abstract Doc Link 17764839 Disease Relevance 0.45 Pain Relevance 0.46
Moreover, the protein level of RhoA in BSMs of the AHR mice was significantly increased (Fig. 4).
Positive_regulation (increased) of RhoA
18) Confidence 0.43 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.29 Pain Relevance 0.13
It is thus likely that ACh stimulation activates the upregulated RhoA (Fig. 5), resulting in a greater phosphorylation of MLC (Fig. 6) and contraction of BSMs in AHR mice.
Positive_regulation (activates) of RhoA
19) Confidence 0.43 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.43 Pain Relevance 0.19
Thus, the current study demonstrated an augmentation of ACh-induced, RhoA-mediated Ca2+ sensitization of BSM contraction, which coincides with enhanced protein expression of RhoA, in antigen-induced AHR.
Positive_regulation (augmentation) of RhoA
20) Confidence 0.43 Published 2005 Journal Respir Res Section Body Doc Link PMC545934 Disease Relevance 0.31 Pain Relevance 0.11

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