INT106065

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Context Info
Confidence 0.57
First Reported 2002
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 27
Total Number 27
Disease Relevance 12.69
Pain Relevance 3.97

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

mitochondrion (MAP2K1) Golgi apparatus (MAP2K1) cytoplasm (MAP2K1)
cytosol (MAP2K1) signal transduction (MAP2K1) mitosis (MAP2K1)
Anatomy Link Frequency
SH-SY5Y 2
neuronal 1
colon 1
pore 1
MAP2K1 (Homo sapiens)
Pain Link Frequency Relevance Heat
antagonist 54 99.80 Very High Very High Very High
Morphine 10 98.86 Very High Very High Very High
bradykinin 12 98.64 Very High Very High Very High
aspirin 9 97.28 Very High Very High Very High
cINOD 6 94.44 High High
Paracetamol 9 90.88 High High
member 8 1 87.68 High High
Ventral tegmentum 1 76.80 Quite High
Locus ceruleus 1 75.36 Quite High
orphanin 4 75.00 Quite High
Disease Link Frequency Relevance Heat
Rheumatoid Arthritis 402 99.36 Very High Very High Very High
Apoptosis 672 98.84 Very High Very High Very High
Carcinoma 580 98.74 Very High Very High Very High
Neuroblastoma 353 96.82 Very High Very High Very High
Cancer 241 96.72 Very High Very High Very High
Colon Cancer 18 95.52 Very High Very High Very High
INFLAMMATION 48 93.72 High High
Death 67 91.84 High High
Polyps 1 89.76 High High
Stress 10 86.08 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Clonidine, an inhibitor of p38MAPK and MEK1/2, inhibited the expression of VEGF protein and mRNA in the RPE cells stimulated with IL-1beta.
Negative_regulation (inhibitor) of MEK1
1) Confidence 0.57 Published 2009 Journal Graefes Arch. Clin. Exp. Ophthalmol. Section Body Doc Link 19011889 Disease Relevance 0 Pain Relevance 0
Selective inhibitors of MEK1/ERK44/42 and p38 mitogen-activated protein kinases potentiate apoptosis induction by sulindac sulfide in human colon carcinoma cells.
Negative_regulation (inhibitors) of MEK1 in colon associated with colon cancer and apoptosis
2) Confidence 0.57 Published 2005 Journal Mol. Cancer Ther. Section Title Doc Link 15657353 Disease Relevance 0.77 Pain Relevance 0.27
Apoptosis was unaffected by inhibitors of the mitochondrial permeability transition pore and by inhibitors of Jun NH(2)-terminal kinases, p38 mitogen-activated protein kinase, or mitogen-activated protein kinase kinase 1/2.
Negative_regulation (inhibitors) of mitogen-activated protein kinase kinase 1 in pore associated with apoptosis
3) Confidence 0.57 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15665138 Disease Relevance 1.41 Pain Relevance 0.72
Since U0126, a specific inhibitor for MEK1/2, also induced a partial G1/S arrest, the G1/S arrest induced by indomethacin is, at least in part, caused by the inhibition of ERK1/2.
Negative_regulation (inhibitor) of MEK1
4) Confidence 0.42 Published 2005 Journal Oncogene Section Abstract Doc Link 15735687 Disease Relevance 0.28 Pain Relevance 0.07
CONCLUSIONS: The effect of clonidine on the expression of VEGF may be via suppression of the p38MAPK and MEK1/2 signal transduction pathways activated with IL-1beta.


Negative_regulation (suppression) of MEK1
5) Confidence 0.41 Published 2009 Journal Graefes Arch. Clin. Exp. Ophthalmol. Section Body Doc Link 19011889 Disease Relevance 0 Pain Relevance 0
Both aspirin-mediated permeability and phosphorylation of p38 MAPK were significantly attenuated by SB-203580 (a p38 MAPK inhibitor) but not by U-0126 (a MEK1 inhibitor) or SP-600125 (a JNK inhibitor).
Negative_regulation (inhibitor) of MEK1 associated with aspirin
6) Confidence 0.35 Published 2008 Journal Am. J. Physiol., Cell Physiol. Section Abstract Doc Link 18667601 Disease Relevance 0.13 Pain Relevance 0.39
In the current study, MEK1 inhibition by PD98059 with or without downregulation of Mcl-1 did not induce significant apoptosis rates in Huh7 cells.
Negative_regulation (inhibition) of MEK1 associated with apoptosis
7) Confidence 0.28 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 1.03 Pain Relevance 0
Here we observed that ATRA also induces ERK1/2 phosphorylation in SH-SY5Y human neuroblastoma cells (Figure 2c, right) and we confirmed the key role of ERK1/2 phosphorylation for COX-2 up-regulation by ATRA since treatment with PD098059, the selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK-1), was sufficient to abrogate COX-2 promoter activation, to increase COX-2 protein expression and to increase PGE2 production (Figure 2d and Figure 3a right and 3b).
Negative_regulation (inhibitor) of MEK-1 in SH-SY5Y associated with neuroblastoma
8) Confidence 0.26 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC1769480 Disease Relevance 0.21 Pain Relevance 0
Here we observed that ATRA also induces ERK1/2 phosphorylation in SH-SY5Y human neuroblastoma cells (Figure 2c, right) and we confirmed the key role of ERK1/2 phosphorylation for COX-2 up-regulation by ATRA since treatment with PD098059, the selective inhibitor of mitogen-activated protein kinase kinase 1 (MEK-1), was sufficient to abrogate COX-2 promoter activation, to increase COX-2 protein expression and to increase PGE2 production (Figure 2d and Figure 3a right and 3b).
Negative_regulation (inhibitor) of mitogen-activated protein kinase kinase 1 in SH-SY5Y associated with neuroblastoma
9) Confidence 0.26 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC1769480 Disease Relevance 0.21 Pain Relevance 0
As in Hep3B cells, we found that MEK1 inhibition did not influence Mcl-1 expression in these cell lines (Fig. 2A).
Negative_regulation (inhibition) of MEK1
10) Confidence 0.21 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 0.92 Pain Relevance 0
Mcl-1 downregulation, however, when combined with MEK1 inhibition and chemotherapy, triggered apoptosis in Huh7 cells.
Negative_regulation (inhibition) of MEK1 associated with apoptosis
11) Confidence 0.21 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 1.03 Pain Relevance 0
Enhanced apoptosis sensitivity of Mcl-1 expressing HCC cells to chemotherapy after inhibition of PI3K, but not after inhibition of Jak2, mTOR, MEK1, Src or Raf I kinase
Negative_regulation (inhibition) of MEK1 associated with carcinoma and apoptosis
12) Confidence 0.21 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 0.91 Pain Relevance 0.06
In a previous study of our group, inhibition of MEK1 by PD98059 in Hep3B cells neither influenced Mcl-1 expression nor sensitized to bleomycin-induced apoptosis (300 ?
Negative_regulation (inhibition) of MEK1 associated with apoptosis
13) Confidence 0.21 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 0.93 Pain Relevance 0
Neither Mcl-1 expression nor chemotherapeutic drug-induced apoptosis (as tested for cisplatin, epirubicin and 5-FU) was influenced by MEK1 inhibition (Fig. 2A, 2B, and data not shown).
Negative_regulation (inhibition) of MEK1 associated with apoptosis
14) Confidence 0.21 Published 2006 Journal BMC Cancer Section Body Doc Link PMC1601962 Disease Relevance 0.98 Pain Relevance 0
The high basal level phosphorylation of ERK was abrogated by treatment with U0126, an inhibitor for MEK1 (Fig. 5C), suggesting a constitutive activation of the MAPK pathway upstream of ERK in these metaplastic cells.
Negative_regulation (inhibitor) of MEK1
15) Confidence 0.20 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1289280 Disease Relevance 0.52 Pain Relevance 0.03
ATRA-induced COX-2 protein expression and PGE2 production are inhibited by RAR pan-antagonist LE540 or MEK-1 inhibitor PD98059
Negative_regulation (inhibitor) of MEK-1 associated with antagonist
16) Confidence 0.19 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC1769480 Disease Relevance 0.12 Pain Relevance 0.20
ATRA increases the activity of the human COX-2 promoter and its effect is inhibited by RAR-pan-antagonist LE540 or MEK-1 inhibitor PD98059
Negative_regulation (inhibitor) of MEK-1 associated with antagonist
17) Confidence 0.19 Published 2007 Journal J Neuroinflammation Section Body Doc Link PMC1769480 Disease Relevance 0.30 Pain Relevance 0.11
Furthermore, previous studies have demonstrated that U0126 inhibits MEK1 and MEK2, and PD98059 [29] inhibits MEK1, but only inefficiently inhibits MEK2 [40].
Negative_regulation (inhibits) of MEK1
18) Confidence 0.19 Published 2010 Journal Nutrition Research and Practice Section Body Doc Link PMC2933444 Disease Relevance 0.31 Pain Relevance 0
It has been reported previously that U0126 directly inhibits MEK1/2 activity, whereas PD 98059 does not directly inhibit MEK1 activity but does inhibit its activation (phosphorylation) by Raf-1 [29].
Negative_regulation (inhibit) of MEK1
19) Confidence 0.19 Published 2010 Journal Nutrition Research and Practice Section Body Doc Link PMC2933444 Disease Relevance 0.32 Pain Relevance 0
Furthermore, previous studies have demonstrated that U0126 inhibits MEK1 and MEK2, and PD98059 [29] inhibits MEK1, but only inefficiently inhibits MEK2 [40].
Negative_regulation (inhibits) of MEK1
20) Confidence 0.19 Published 2010 Journal Nutrition Research and Practice Section Body Doc Link PMC2933444 Disease Relevance 0.31 Pain Relevance 0

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