INT178116

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Context Info
Confidence 0.80
First Reported 2004
Last Reported 2008
Negated 2
Speculated 0
Reported most in Body
Documents 7
Total Number 18
Disease Relevance 4.09
Pain Relevance 0.74

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transport (GJA1) Golgi apparatus (GJA1) endoplasmic reticulum (GJA1)
cell-cell signaling (GJA1) cytoplasm (GJA1) signal transducer activity (GJA1)
Anatomy Link Frequency
smooth muscle 3
myocytes 2
myometrium 1
interstitial cells 1
smooth muscle cells 1
GJA1 (Homo sapiens)
Pain Link Frequency Relevance Heat
Kinase C 15 99.78 Very High Very High Very High
Dismenorea 63 97.16 Very High Very High Very High
metalloproteinase 24 93.16 High High
Action potential 12 69.52 Quite High
antagonist 105 67.20 Quite High
analgesia 6 9.36 Low Low
Pain 18 7.08 Low Low
agonist 15 5.00 Very Low Very Low Very Low
withdrawal 12 5.00 Very Low Very Low Very Low
nociceptor 6 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Hypertrophy 12 99.68 Very High Very High Very High
Endometriosis (extended) 12 98.56 Very High Very High Very High
Cancer 195 98.42 Very High Very High Very High
Ovarian Cancer 69 98.12 Very High Very High Very High
Dysmenorrhea 63 97.16 Very High Very High Very High
Skin Cancer 42 95.20 Very High Very High Very High
Malignant Neoplastic Disease 18 80.24 Quite High
Toxicity 12 80.12 Quite High
Abruptio Placentae 12 80.08 Quite High
Adhesions 12 78.24 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Using the specific antibody directed against unphosphorylated connexin 43, we have shown that it is MICs and not smooth myocytes that continually express this connexin 43, and that this connexin 43 is distributed evenly throughout the MIC cell membrane in its unphosphorylated form.
Phosphorylation (unphosphorylated) of connexin 43 in myocytes
1) Confidence 0.80 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0.18 Pain Relevance 0.22
Of particular interest, hemichannel function appears to be controlled by protein kinase C dependant phosphorylation of connexin 43 at serine residue 368 with the unphosphorylated state resulting in increased permeability [24].
Phosphorylation (phosphorylation) of connexin 43 associated with kinase c
2) Confidence 0.80 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0.05
In contrast to total connexin 43, unphosphorylated connexin 43 was confined to the cells described above, located mainly on the boundary of the smooth muscle bundles and in the fibromuscular septum in all of the biopsies examined (Figure 2a).
Phosphorylation (unphosphorylated) of connexin 43 in smooth muscle
3) Confidence 0.80 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0
The appearance, number and location of the cells that we identified by staining for unphosphorylated connexin 43 and c-kit correspond most probably with MICs.
Phosphorylation (unphosphorylated) of connexin 43
4) Confidence 0.80 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0
In all biopsies from pregnant women in labour or prior to labour, the antibody for unphosphorylated connexin 43 did not bind to the smooth myocytes.
Phosphorylation (unphosphorylated) of connexin 43 in myocytes
5) Confidence 0.80 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0
Monoclonal mouse anti-human antibody to unphosphorylated connexin 43 (Cat no: 13-8300, dilution 1/100, Zymed, San Francisco, California) was added for 30 minutes and rinsed with phosphate buffered saline (PBS) before adding polyclonal rabbit anti-mouse biotinylated immunoglobulin (dilution 1/400, DakoCytomation, Heverlee, Belgium).
Neg (no) Phosphorylation (unphosphorylated) of connexin 43
6) Confidence 0.79 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0.21 Pain Relevance 0
In this regard it is interesting to note that activation of MAPK1 in pregnant rat myometrium leads to phosphorylation of GJA1 at Ser-255 and this causes a loss of amplitude and synchronization of uterine contractions [41].
Phosphorylation (phosphorylation) of GJA1 in uterine associated with dismenorea
7) Confidence 0.76 Published 2007 Journal BMC Pregnancy Childbirth Section Body Doc Link PMC1892059 Disease Relevance 0.10 Pain Relevance 0.10
On the other hand phosphorylation of GJA1 and other connexins may also trigger internalization and degradation [40].
Phosphorylation (phosphorylation) of GJA1
8) Confidence 0.76 Published 2007 Journal BMC Pregnancy Childbirth Section Body Doc Link PMC1892059 Disease Relevance 0.08 Pain Relevance 0.08
Although this architecture was less apparent in samples from postmenopausal women, unphosphorylated connexin 43 expressing cells were still identifiable as separate from smooth muscle cells that did not express connexin 43 (data not shown).
Phosphorylation (unphosphorylated) of connexin 43 in smooth muscle cells
9) Confidence 0.61 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0.18 Pain Relevance 0
In biopsies taken from non-pregnant pre-menopausal women the smooth muscle bundles showed less hypertrophy making rows of unphosphorylated connexin 43 expressing cells more easily visible (data not shown).
Phosphorylation (unphosphorylated) of connexin 43 in smooth muscle associated with hypertrophy and endometriosis (extended)
10) Confidence 0.61 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0.20 Pain Relevance 0
This indicates that the cells that bind unphosphorylated connexin 43 are likely to be MICs.
Phosphorylation (unphosphorylated) of connexin 43
11) Confidence 0.61 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0
This paper describes the topographical distribution of MICs by using single stain immunohistochemistry and double stain indirect immunofluorescence techniques with a combination of five antibodies; unphosphorylated connexin 43 (binds only when the serine at residue 368 is unphosphorylated), total connexin 43 (independent of phosphorylation status), KIT (a membrane bound tyrosine kinase receptor found on interstitial cells of Cajal) [10], alpha smooth muscle actin (a smooth muscle marker), and prolyl 4-hydroxylase (a specific marker for fibroblasts) [11].
Neg (independent) Phosphorylation (phosphorylation) of connexin 43 in smooth muscle
12) Confidence 0.61 Published 2008 Journal Reprod Biol Endocrinol Section Body Doc Link PMC2553078 Disease Relevance 0.07 Pain Relevance 0.07
Single stain immunohistochemical and double stain immunofluorescence techniques visualised antibodies directed against total connexin 43, unphosphorylated connexin 43, KIT, alpha-SMA and prolyl 4-hydroxylase in myometrial biopsies from 26 women representing all stages of reproductive life.


Phosphorylation (unphosphorylated) of connexin 43
13) Confidence 0.61 Published 2008 Journal Reprod Biol Endocrinol Section Abstract Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0
Immunohistochemistry using an antibody to unphosphorylated connexin 43 to identify human myometrial interstitial cells

Background

Phosphorylation (unphosphorylated) of connexin 43 in interstitial cells
14) Confidence 0.61 Published 2008 Journal Reprod Biol Endocrinol Section Title Doc Link PMC2553078 Disease Relevance 0 Pain Relevance 0
A better understanding of the pathways that regulate GJA1 expression and phosphorylation in human myometrium should clarify the role of these proteins during pregnancy and labour.
Phosphorylation (phosphorylation) of GJA1 in myometrium
15) Confidence 0.59 Published 2007 Journal BMC Pregnancy Childbirth Section Body Doc Link PMC1892059 Disease Relevance 0.09 Pain Relevance 0.09
The tumor growth inhibition induced by ABT-627, was also associated with a reduction of Cx43 phosphorylation and with an increase Cx43-based intercellular communication, suggesting that ETAR blockade may contribute to the control of ovarian carcinoma growth and progression also by preventing the loss of GJIC [29].
Phosphorylation (phosphorylation) of Cx43 associated with cancer and ovarian cancer
16) Confidence 0.25 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 1.09 Pain Relevance 0
In this regards ET-1 and ET-3 by ETBR signalling induce the inactivation of the gap junctions through the phosphorylation of the Cx43, which are responsible for contact mediated regulatory control of keratinocytes.
Phosphorylation (phosphorylation) of Cx43 in keratinocytes
17) Confidence 0.25 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 1.03 Pain Relevance 0.08
In ovarian carcinoma cells, ET-1 via ETAR induces a transient and a dose-dependent reduction of GJIC (50–75%) and phosphorylates Cx43 through Src tyrosine kinase pathway indicating that ET-1 promotes cellular uncoupling at the level of connexin maturation and subsequent degradation [29].
Phosphorylation (phosphorylates) of Cx43 associated with ovarian cancer
18) Confidence 0.19 Published 2004 Journal J Transl Med Section Body Doc Link PMC436068 Disease Relevance 0.85 Pain Relevance 0.06

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