INT83708

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Context Info
Confidence 0.57
First Reported 1999
Last Reported 2011
Negated 1
Speculated 0
Reported most in Abstract
Documents 156
Total Number 158
Disease Relevance 84.93
Pain Relevance 27.85

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

nucleoplasm (MAPK1) mitochondrion (MAPK1) Golgi apparatus (MAPK1)
DNA binding (MAPK1) protein complex (MAPK1) response to stress (MAPK1)
Anatomy Link Frequency
T cells 7
colon 6
fibroblasts 2
HPAF-II 2
apoptotic cell 2
MAPK1 (Homo sapiens)
Pain Link Frequency Relevance Heat
bradykinin 240 99.98 Very High Very High Very High
cINOD 253 99.84 Very High Very High Very High
chemokine 42 99.84 Very High Very High Very High
withdrawal 40 99.82 Very High Very High Very High
Inflammation 1375 99.58 Very High Very High Very High
antagonist 47 99.32 Very High Very High Very High
agonist 120 99.28 Very High Very High Very High
cytokine 1148 99.12 Very High Very High Very High
dorsal root ganglion 77 99.12 Very High Very High Very High
opiate 17 99.12 Very High Very High Very High
Disease Link Frequency Relevance Heat
Pancreatic Cancer 33 100.00 Very High Very High Very High
Stress 567 99.96 Very High Very High Very High
Apoptosis 1018 99.88 Very High Very High Very High
Infection 210 99.82 Very High Very High Very High
Liver Cancer 15 99.80 Very High Very High Very High
INFLAMMATION 1514 99.72 Very High Very High Very High
Disease 1137 99.66 Very High Very High Very High
Hepatocellular Cancer 137 99.66 Very High Very High Very High
Eosinophilia 22 99.64 Very High Very High Very High
Lung Injury 13 99.60 Very High Very High Very High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Inhibition of extracellular-signal regulated kinases 1/2 is required for apoptosis of human colon cancer cells in vitro by sulindac metabolites.
Negative_regulation (Inhibition) of extracellular-signal regulated kinases 1/2 in colon associated with colon cancer and apoptosis
1) Confidence 0.57 Published 2004 Journal Cancer Res. Section Title Doc Link 15548677 Disease Relevance 1.21 Pain Relevance 0.19
PD98059 (a specific inhibitor of MEKK), but not SB203580 (a specific inhibitor of p38 kinase), attenuated PGE(2) (not SP-NO) induced HO-1 protein.
Negative_regulation (inhibitor) of p38
2) Confidence 0.57 Published 2002 Journal J. Cell. Biochem. Section Abstract Doc Link 12112002 Disease Relevance 0.34 Pain Relevance 0.22
The SB203580, a p38 MAP kinase inhibitor, reduced indomethacin-induced cell death by 43%, while PD098059, a MAPK/ERK kinase (MEK)1 inhibitor, did not affect cell death. p38 MAP kinase and caspase-3 activation were not significantly interlinked in indomethacin-induced apoptosis.
Negative_regulation (inhibitor) of ERK associated with apoptosis and death
3) Confidence 0.57 Published 2001 Journal Int J Colorectal Dis Section Abstract Doc Link 11459290 Disease Relevance 0.97 Pain Relevance 0.42
Notably, pronounced downregulations of phosphorylated MEK (85%) and ERK1/2 (pERK1: 81%; pERK2: 80%) were quantitated in brains of opiate addicts.
Negative_regulation (downregulations) of ERK in brains associated with opiate
4) Confidence 0.57 Published 2004 Journal J. Neurochem. Section Abstract Doc Link 15198681 Disease Relevance 0.47 Pain Relevance 0.87
U0126, a specific inhibitor of the ERK-activating kinases MEK-1/-2, prevented the activation of ERK induced by NS-398 and blocked the increase in COX-2 protein expression seen when HT29 cells were treated with NS-398 alone.
Negative_regulation (inhibitor) of ERK-activating
5) Confidence 0.56 Published 2002 Journal Int. J. Cancer Section Abstract Doc Link 11992399 Disease Relevance 0.62 Pain Relevance 0.26
The decreased phosphorylation of extracellular signal-regulated kinase (ERK) was induced by JEV infection and the decrease in ERK was reversed by salicylate.
Negative_regulation (decrease) of ERK associated with infection
6) Confidence 0.56 Published 2002 Journal J. Gen. Virol. Section Abstract Doc Link 12124453 Disease Relevance 0.67 Pain Relevance 0.53
Selective inhibitors of ERK, p38 MAPK, and JNK suppressed the induction of GRP78, CHOP, and PPAR-beta, attenuated indomethacin-induced cytotoxicity and reduced increased caspase activity.
Negative_regulation (inhibitors) of ERK
7) Confidence 0.51 Published 2007 Journal Eur. J. Pharmacol. Section Abstract Doc Link 17341418 Disease Relevance 0.85 Pain Relevance 0.11
We found that indomethacin strongly reduced the basal level of extracellular signal-regulated kinases 1 and 2 (ERK1/2) in HT-29 human colon carcinoma cells.
Negative_regulation (reduced) of extracellular signal-regulated kinases 1 and 2 in colon associated with colon cancer
8) Confidence 0.51 Published 2005 Journal Oncogene Section Abstract Doc Link 15735687 Disease Relevance 0.27 Pain Relevance 0.09
This effect of MCC-555 on the ARE-mediated mRNA degradation was inhibited by extracellular signal-regulated kinase (ERK) pathway inhibitors.
Negative_regulation (inhibitors) of ERK
9) Confidence 0.51 Published 2006 Journal Mol. Cancer Ther. Section Abstract Doc Link 16731769 Disease Relevance 0.60 Pain Relevance 0.07
This effect of MCC-555 on the ARE-mediated mRNA degradation was inhibited by extracellular signal-regulated kinase (ERK) pathway inhibitors.
Negative_regulation (inhibitors) of extracellular signal-regulated kinase
10) Confidence 0.51 Published 2006 Journal Mol. Cancer Ther. Section Abstract Doc Link 16731769 Disease Relevance 0.61 Pain Relevance 0.07
Furthermore, both SB203580 (an inhibitor of p38 mitogen-activated protein kinase [MAPK]) and PD98059 (an inhibitor of MEK, upstream of ERK) attenuated the BK-induced IL-6 and PGE(2) synthesis.
Negative_regulation (inhibitor) of ERK associated with bradykinin
11) Confidence 0.51 Published 2004 Journal Biochem. Pharmacol. Section Abstract Doc Link 15345332 Disease Relevance 0.30 Pain Relevance 0.63
Interestingly, treatment with SB203580, the p38 MAPK inhibitor, also mitigated fMLP-induced superoxide anion generation and p38 MAPK and p47(phox) phosphorylation as well as apoptosis in a concentration-dependent fashion in neutrophils.
Negative_regulation (inhibitor) of p38 in neutrophils associated with apoptosis
12) Confidence 0.50 Published 2010 Journal Clin. Exp. Immunol. Section Abstract Doc Link 20345980 Disease Relevance 0.10 Pain Relevance 0.40
This effect is mediated by NSAID-induced inhibition of MAPK (ERK2) kinase signaling pathway, essential for cell proliferation.
Negative_regulation (inhibition) of ERK2 associated with cinod
13) Confidence 0.49 Published 2001 Journal Life Sci. Section Abstract Doc Link 11758830 Disease Relevance 0.87 Pain Relevance 0.59
Both NSAIDs also significantly inhibited ERK2 activity: IND >53% inhibition, NS-398, 100 microM >72% inhibition; all p<0.05.
Negative_regulation (inhibited) of ERK2 associated with cinod
14) Confidence 0.49 Published 2001 Journal Life Sci. Section Abstract Doc Link 11758830 Disease Relevance 0.98 Pain Relevance 0.62
As expected, the ERK activity was reduced by treatment in both normal and carcinoma cells with U0126 which correlates with the suppression of DNA synthesis observed (Fig. 5C).
Negative_regulation (reduced) of ERK associated with carcinoma
15) Confidence 0.46 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1289280 Disease Relevance 0.31 Pain Relevance 0.11
IL6 was also inhibited by SB-203580, a p38 MAPK inhibitor, in IL1B treated broblast-like synoviocytes (FLS) cells [31].
Negative_regulation (inhibitor) of p38 MAPK
16) Confidence 0.46 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2855702 Disease Relevance 0.78 Pain Relevance 0.44
Both the sulfide and sulfone metabolites of sulindac as well as more potent cyclic GMP-dependent phosphodiesterase inhibitors were shown to cause inhibition of extracellular signal-regulated kinase (ERK)1/2 phosphorylation at doses (40-600 microM) and times (1-5 days) consistent with the induction of apoptosis by the drugs.
Negative_regulation (inhibition) of ERK associated with apoptosis
17) Confidence 0.43 Published 2001 Journal Cancer Res. Section Abstract Doc Link 11245463 Disease Relevance 0.93 Pain Relevance 0.19
This taurine-stimulated ERK 1/2 activation was inhibited by PD98059.
Negative_regulation (inhibited) of ERK
18) Confidence 0.43 Published 2007 Journal FEBS Lett. Section Abstract Doc Link 18036343 Disease Relevance 0.26 Pain Relevance 0.10
We further demonstrate that both a free radical scavenger and an inhibitor of p38 mitogen-activated protein kinase (MAPK) reduce IL-1beta-induced synthesis of COX-2.
Negative_regulation (inhibitor) of p38
19) Confidence 0.42 Published 2000 Journal J. Neurochem. Section Abstract Doc Link 11032891 Disease Relevance 0.49 Pain Relevance 0.12
Wortmannin, an inhibitor of phosphatidylinositol-3 kinase, or SB203580, an inhibitor of p38 MAP kinase, did not reduce AAP-induced toxicity, indicating that these enzymes do not play a major role in cell toxicity.
Negative_regulation (inhibitor) of p38 associated with toxicity and paracetamol
20) Confidence 0.42 Published 2001 Journal Mol. Pharmacol. Section Abstract Doc Link 11562448 Disease Relevance 0.89 Pain Relevance 0.78

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