INT165800

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Context Info
Confidence 0.67
First Reported 2003
Last Reported 2011
Negated 0
Speculated 0
Reported most in Body
Documents 17
Total Number 18
Disease Relevance 11.69
Pain Relevance 1.21

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

aging (Ddit3) nucleus (Ddit3) cell cycle (Ddit3)
DNA binding (Ddit3) transcription factor binding (Ddit3) cytoplasm (Ddit3)
Anatomy Link Frequency
neurons 2
reticulum 1
Ddit3 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
Inflammation 19 93.80 High High
Glutamate receptor 2 91.72 High High
ischemia 68 89.20 High High
Glutamate 29 86.52 High High
Neurotransmitter 2 84.36 Quite High
excitatory amino acid 4 83.16 Quite High
Paracetamol 1 81.56 Quite High
agonist 15 67.92 Quite High
nMDA receptor 4 56.96 Quite High
anesthesia 10 48.88 Quite Low
Disease Link Frequency Relevance Heat
Apoptosis 94 100.00 Very High Very High Very High
Stress 335 99.98 Very High Very High Very High
Diabetic Retinopathy 44 98.92 Very High Very High Very High
Death 95 98.44 Very High Very High Very High
Diabetes Mellitus 60 97.60 Very High Very High Very High
Neuroblastoma 23 97.32 Very High Very High Very High
INFLAMMATION 21 93.80 High High
Cv Unclassified Under Development 60 89.20 High High
Drug Induced Neurotoxicity 101 86.64 High High
Hepatotoxicity 7 83.68 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
They demonstrated to be caused by an accumulation of polyubiquitinated proteins and increases in X box binding protein (XBP-1) mRNA splicing and C/EBP-homologous (CHOP) mRNA, representing activation of the unfolded-protein response (UPR) signaling pathway.
Positive_regulation (accumulation) of C/EBP-homologous
1) Confidence 0.67 Published 2007 Journal Molecular Vision Section Body Doc Link PMC2652022 Disease Relevance 1.86 Pain Relevance 0.28
Here, the upregulation of GADD153 was observed after mefloquine treatment in NG108 cells (10 ?
Positive_regulation (upregulation) of GADD153
2) Confidence 0.65 Published 2003 Journal Malar J Section Body Doc Link PMC152658 Disease Relevance 0.39 Pain Relevance 0.04
In preliminary experiments utilizing primary rat neurons, we have also observed an upregulation of GADD153 after mefloquine treatment (unpublished data).
Positive_regulation (upregulation) of GADD153 in neurons
3) Confidence 0.65 Published 2003 Journal Malar J Section Body Doc Link PMC152658 Disease Relevance 0.35 Pain Relevance 0.04
The unfolded protein response is characterized by generalized suppression of protein synthesis and the specific induction of ER-resident proteins and GADD153 [24].
Positive_regulation (induction) of GADD153
4) Confidence 0.65 Published 2003 Journal Malar J Section Body Doc Link PMC152658 Disease Relevance 0.47 Pain Relevance 0.04
In neurons, GADD153 is selectively upregulated under conditions of endoplasmic reticulum (ER) stress arising from depletion of calcium stores [26].
Positive_regulation (upregulated) of GADD153 in reticulum associated with stress
5) Confidence 0.65 Published 2003 Journal Malar J Section Body Doc Link PMC152658 Disease Relevance 0.41 Pain Relevance 0.05
CHOP can be induced in response to cellular stress, especially ER stress, and is involved in the ER stress-induced apoptosis pathway (Zinszner et al. 1998).
Positive_regulation (induced) of CHOP associated with stress and apoptosis
6) Confidence 0.58 Published 2010 Journal Acta Orthopaedica Section Body Doc Link PMC2895349 Disease Relevance 1.83 Pain Relevance 0.20
Mefloquine caused a striking upregulation of growth arrest and development protein 153 (GADD153), a transcription factor selectively modulated under conditions of ER stress [8].
Positive_regulation (upregulation) of GADD153 associated with stress
7) Confidence 0.52 Published 2003 Journal Malar J Section Body Doc Link PMC194860 Disease Relevance 0.33 Pain Relevance 0
The ATF4 and XBP1 proteins are transcriptional enhancers of the CHOP gene.
Positive_regulation (enhancers) of CHOP
8) Confidence 0.48 Published 2010 Journal Acta Orthopaedica Section Body Doc Link PMC2895349 Disease Relevance 0.50 Pain Relevance 0.04
They demonstrated to be caused by an accumulation of polyubiquitinated proteins and increases in X box binding protein (XBP-1) mRNA splicing and C/EBP-homologous (CHOP) mRNA, representing activation of the unfolded-protein response (UPR) signaling pathway.
Positive_regulation (increases) of C/EBP-homologous
9) Confidence 0.45 Published 2007 Journal Molecular Vision Section Body Doc Link PMC2652022 Disease Relevance 1.77 Pain Relevance 0.28
Whereas either DMF or CCl(4) treatment alone marginally changed the expression levels of glucose-regulated protein 78 and 94 and phosphorylated PKR-like ER-localized eIF2alpha kinase, concomitant treatment with DMF and CCl(4) synergistically induced them with increases in glucose-regulated protein 78 and C/EBP homologous protein mRNAs.
Positive_regulation (increases) of C/EBP homologous protein
10) Confidence 0.45 Published 2010 Journal Chem. Biol. Interact. Section Abstract Doc Link 20097184 Disease Relevance 0.60 Pain Relevance 0.08
Based on RT-PCR, mefloquine upregulated cJun, IkappaB and GADD153.
Positive_regulation (upregulated) of GADD153
11) Confidence 0.44 Published 2003 Journal Malar J Section Abstract Doc Link PMC152658 Disease Relevance 0.15 Pain Relevance 0
The upregulation of GADD153 by mefloquine suggests that the drug might affect the function of the ER in neurons, perhaps by disruption of calcium homeostasis.


Positive_regulation (upregulation) of GADD153 in neurons
12) Confidence 0.44 Published 2003 Journal Malar J Section Body Doc Link PMC152658 Disease Relevance 0.18 Pain Relevance 0
The third component to the UPR cascade is an induction of the ER transcription factor GADD153 [11,12], an effect also observed after mefloquine treatment.
Positive_regulation (induction) of GADD153
13) Confidence 0.38 Published 2003 Journal Malar J Section Body Doc Link PMC194860 Disease Relevance 0.09 Pain Relevance 0
The second, the unfolded protein response (UPR) induces three divergent cellular events: (i) the activation of transcription factor ATF6 leading to the upregulation of ER chaperones such as protein disulfide isomerase, (ii) upregulation of the pro-apoptotic transcription factor GADD153 and (iii) suppression of protein synthesis via phosphorylation of eukaryotic translation initiation factor 2?
Positive_regulation (upregulation) of GADD153 associated with apoptosis
14) Confidence 0.38 Published 2003 Journal Malar J Section Body Doc Link PMC194860 Disease Relevance 0.51 Pain Relevance 0.08
Upregulation of the ER chaperones, GADD153 and PERK in response to a toxic insult would constitute direct evidence of an ER stress response.
Positive_regulation (Upregulation) of GADD153 associated with stress
15) Confidence 0.35 Published 2003 Journal Malar J Section Body Doc Link PMC194860 Disease Relevance 0.48 Pain Relevance 0.07
Secondly, mefloquine has been shown to cause a striking upregulation of GADD153, a transcription factor selectively modulated under conditions of ER stress [8].
Positive_regulation (upregulation) of GADD153 associated with stress
16) Confidence 0.35 Published 2003 Journal Malar J Section Body Doc Link PMC194860 Disease Relevance 0.34 Pain Relevance 0
Our previous study showed that the level of ER stress-induced transcription factor CHOP was remarkably increased during the early stage of DR [3].
Positive_regulation (increased) of CHOP associated with stress and diabetic retinopathy
17) Confidence 0.23 Published 2011 Journal Molecular Vision Section Body Doc Link PMC3021576 Disease Relevance 0.71 Pain Relevance 0
Our previous study showed that the level of ER stress-induced transcription factor CHOP was remarkably increased during the early stage of DR [3].
Positive_regulation (induced) of CHOP associated with stress and diabetic retinopathy
18) Confidence 0.23 Published 2011 Journal Molecular Vision Section Body Doc Link PMC3021576 Disease Relevance 0.72 Pain Relevance 0

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