INT234813

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Context Info
Confidence 0.66
First Reported 2008
Last Reported 2010
Negated 2
Speculated 0
Reported most in Body
Documents 58
Total Number 63
Disease Relevance 3.67
Pain Relevance 6.48

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cell differentiation (RAB5A) plasma membrane (RAB5A) GTPase activity (RAB5A)
Anatomy Link Frequency
upper 5
plasma 3
band 2
vesicles 2
macrophages 1
RAB5A (Homo sapiens)
Pain Link Frequency Relevance Heat
agonist 5830 99.84 Very High Very High Very High
imagery 397 99.54 Very High Very High Very High
Dopamine 55 98.92 Very High Very High Very High
cytokine 2 93.12 High High
dopamine receptor 55 5.00 Very Low Very Low Very Low
cINOD 55 5.00 Very Low Very Low Very Low
ischemia 55 5.00 Very Low Very Low Very Low
Pain 8 5.00 Very Low Very Low Very Low
cva 6 5.00 Very Low Very Low Very Low
headache 6 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Infection 504 99.56 Very High Very High Very High
Salmonella Infection 2 79.20 Quite High
Stroke 165 73.04 Quite High
Viral Infection 2 70.40 Quite High
Death 8 57.76 Quite High
Dengue 66 50.00 Quite Low
Hemophagocytic Lymphohistiocytosis 4 46.96 Quite Low
Syndrome 42 43.96 Quite Low
General Immunology 2 42.44 Quite Low
Congenital Anomalies 6 37.12 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
In contrast to that observed with certain other GPCRs [33,35], over-expression of Rab5aS34N did not appear to substantially reduce cicaprost-induced internalization of the hIP when assessed through the ELISA-based internalization assays.
Gene_expression (over) of Rab5aS34N
1) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.16
Failure to detect corresponding agonist-dependent increases in Rab5 expression in the P100 fractions owing to its translocation from the S100 fractions, except at the 2 h time point, was most likely simply due to the saturation of the chemiluminescence detection system owing to the already high levels of Rab5 associated with the P100 fraction, even in the absence of agonist.
Gene_expression (expression) of Rab5 associated with agonist
2) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.28
Through ELISA-based assays, it was established that over-expression of Rab5a led to a significant increase in cicaprost-induced internalization throughout the initial 3 h duration post-agonist stimulation but did not interfere with the level of the hIP recycled at the 4 h time point.
Gene_expression (expression) of Rab5a associated with agonist
3) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.22
Whilst there was no change in the overall level of Rab5 protein expression over the duration of cicaprost stimulation, there was a significant decrease in the levels of Rab5 in the S100 fraction as early as 30 min, which continued to decrease to barely detectable levels at 2–3 h post agonist stimulation (Figs. 4A and B).
Gene_expression (expression) of Rab5 associated with agonist
4) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.21
Thereafter, Rab5 expression in the S100 fractions at the various time points was expressed as a percentage of that in the absence of cicaprost (Rab5 Expression in S100; % Expression ± S.E.M., n = 3).


Gene_expression (expression) of Rab5
5) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0.06 Pain Relevance 0
Herein, while expression of DynK44A or Rab5aS34N partially impaired cicaprost-induced hIP internalization, co-expression of both factors together did not lead to further impairments suggesting that dynamin and Rab5 regulate hIP internalization through a common pathway rather than through distinct mechanisms.
Gene_expression (expression) of Rab5aS34N
6) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.11
Conversely over-expression of the constitutively active Rab5aQ79L led to significantly increased cicaprost-induced hIP internalization compared to non-transfected or control cells transfected with pcDNA (p = 0.0005; ANOVA), but Rab5aQ79L did not alter the overall profile or extent of that hIP internalization relative to the wild type Rab5 (Fig. 1G, p = 0.6718).
Gene_expression (expression) of Rab5aQ79L
7) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0
Over-expression of DynK44A and Rab5aS34N in HEK.hIPWT cells was confirmed by western blot analysis (data not shown).
Gene_expression (expression) of Rab5aS34N
8) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0
The fact that there is such abundant expression of endogenous Rab5 in HEK.hIP cells may explain why Rab5aS34N did not result in a more substantial inhibition of internalization of the hIP (Fig. 1F).
Gene_expression (expression) of Rab5
9) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0
These data confirm the specificity of the Rab5 data and, moreover, confirm that the observed decline in Rab5 expression in the S100 fractions owing to its translocation from the cytosolic fractions was indeed a cicaprost-induced event and was not due to lack of uniformity in protein loading, for example.
Gene_expression (expression) of Rab5
10) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.06
Whilst incubation of the cells over-expressing Rab5aS34N with cicaprost for 2 h led to internalization of the hIP, consistent with the ELISA-based internalization studies the extent of relocalization of the hIP away from the plasma membrane was significantly impaired and the pattern of intracellular staining was more diffuse, lacking the distinct vesicular pattern observed in the HEK.hIP cells expressing the wild type Rab5a (Fig. 2B, Anti-HA).
Gene_expression (expressing) of Rab5a in plasma
11) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.15
Moreover, while over-expression of a dominant negative form of Rab5a, namely Rab5aS34N, did not appear to affect the initial rate or overall biphasic profile of cicaprost-induced hIP internalization over the 4 h incubation period, it significantly impaired hIP internalization relative to that of the wild type Rab5a (Fig. 1F; p = 0.0003; ANOVA), with most significance at 2 and 3 h (Fig. 1E; p = 0.05 and p = 0.0001, respectively).
Gene_expression (expression) of Rab5a
12) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.06
Hence, in view of our findings herein involving Rab5, we sought to determine whether expression of DynK44A alone or DynK44A along with Rab5aS34N might affect the overall level of cicaprost-induced hIP internalization.
Gene_expression (expression) of Rab5aS34N
13) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0
Concomitant with this, pre-immunolabelled cell surface hIP internalized in response to cicaprost stimulation into intracellular vesicular endosomes that were markedly increased in size compared to those in cells over-expressing Rab5awt (Fig. 2C, Anti-HA).
Gene_expression (expressing) of Rab5awt
14) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.14
Similarly, while co-expression of both DynK44A along with Rab5aS34N impaired cicaprost-induced internalization in HEK.hIPWT cells relative to pcDNA-transfected cells (Fig. 1H, p < 0.0001; ANOVA), co-expression of both factors together did not significantly impair internalization relative to Rab5aS34N alone (Fig. 1F, p = 0.27; ANOVA) or DynK44A alone (Fig. 1H, p = 0.8068; ANOVA).
Gene_expression (expression) of Rab5aS34N
15) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.06
Moreover, while over-expression of a dominant negative form of Rab5a, namely Rab5aS34N, did not appear to affect the initial rate or overall biphasic profile of cicaprost-induced hIP internalization over the 4 h incubation period, it significantly impaired hIP internalization relative to that of the wild type Rab5a (Fig. 1F; p = 0.0003; ANOVA), with most significance at 2 and 3 h (Fig. 1E; p = 0.05 and p = 0.0001, respectively).
Gene_expression (expression) of Rab5aS34N
16) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.06
The increase in immunoprecipitation of Rab5a in response to agonist was not due to an increase in hIP or Rab5a expression levels (data not shown and Fig. 5; lower panel) or in the level of the hIP present in the anti-HA immunoprecipitates per se (Fig. 5; middle panel) and, hence, was due to enhanced interaction between hIP and Rab5a.
Gene_expression (expression) of Rab5a associated with agonist
17) Confidence 0.66 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.25
The extent of association between the hIP and Rab5aS34N was similar to that of wild type Rab5a (Fig. 5; upper panel) as were the amount of hIP present in the immunoprecipitates and the levels of GFP-Rab5a and -Rab5aS34N over-expression in the HEK.hIP cells (Fig. 5, middle and lower panels, respectively).
Gene_expression (expression) of GFP-Rab5a in upper
18) Confidence 0.57 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.20
In cells over-expressing the dominant negative Rab5aS34N, the pre-immunolabelled hIP was exclusively expressed at the cell surface, as expected, in the absence of agonist stimulation while GFP-Rab5aS34N exhibited diffuse intracellular staining associated with significantly smaller vesicles than those associated with the Rab5aWT (Figs. 2A and B, GFP).
Neg (negative) Gene_expression (expressing) of Rab5aS34N in vesicles associated with agonist
19) Confidence 0.57 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.16
The extent of association between the hIP and Rab5aS34N was similar to that of wild type Rab5a (Fig. 5; upper panel) as were the amount of hIP present in the immunoprecipitates and the levels of GFP-Rab5a and -Rab5aS34N over-expression in the HEK.hIP cells (Fig. 5, middle and lower panels, respectively).
Gene_expression (levels) of GFP-Rab5a in upper
20) Confidence 0.57 Published 2008 Journal Biochim Biophys Acta Section Body Doc Link PMC2680976 Disease Relevance 0 Pain Relevance 0.20

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