INT206950

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Context Info
Confidence 0.45
First Reported 2007
Last Reported 2010
Negated 0
Speculated 0
Reported most in Body
Documents 14
Total Number 15
Disease Relevance 7.02
Pain Relevance 5.71

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

plasma membrane (Atf4) cytoskeleton (Atf4) nucleus (Atf4)
DNA binding (Atf4) microtubule organizing center (Atf4) cytoplasm (Atf4)
Anatomy Link Frequency
liver 1
spinal cord 1
brain 1
limbs 1
Atf4 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
cocaine 2920 99.98 Very High Very High Very High
ischemia 60 98.96 Very High Very High Very High
Spinal cord 62 97.88 Very High Very High Very High
Central nervous system 106 82.44 Quite High
antagonist 10 79.44 Quite High
Paracetamol 1 72.12 Quite High
Dopamine 14 72.08 Quite High
monoamine 30 65.80 Quite High
Neurotransmitter 30 56.72 Quite High
Bile 5 53.40 Quite High
Disease Link Frequency Relevance Heat
Stress 358 99.98 Very High Very High Very High
Injury 152 99.44 Very High Very High Very High
Cv Unclassified Under Development 54 98.96 Very High Very High Very High
Apoptosis 94 94.68 High High
Shock 3 92.00 High High
Lung Injury 14 89.88 High High
Cv General 4 Under Development 2 83.04 Quite High
Repression 21 80.40 Quite High
Increased Venous Pressure Under Development 20 77.68 Quite High
Hepatitis 1 76.52 Quite High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
ATF4 mRNA and XBP1 mRNA, which were present in control rats and had increased markedly in the lungs which limbs underwent 4h of ischemia and 4h of reperfusion.
Positive_regulation (increased) of ATF4 in limbs associated with ischemia
1) Confidence 0.45 Published 2010 Journal Acta Orthopaedica Section Body Doc Link PMC2895349 Disease Relevance 0.52 Pain Relevance 0.05
ATF4 and XBP1 are induced as cell protection mechanisms.
Positive_regulation (induced) of ATF4
2) Confidence 0.45 Published 2010 Journal Acta Orthopaedica Section Body Doc Link PMC2895349 Disease Relevance 1.66 Pain Relevance 0.19
Further, the P450 inhibitors SKF-525A and cimetidine, which have been shown to inhibit N-oxidative metabolism of cocaine, blocked cocaine-induced endogenous ROS generation, translational activation of ATF4, down-regulation of cyclin A, and proliferation inhibition in AF5 cells (Figure 6E–6H).
Positive_regulation (activation) of ATF4 associated with cocaine
3) Confidence 0.44 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.14 Pain Relevance 0.31
0.5 h after exposure to cocaine, preceding induction of ATF4 (Figure 6C).


Positive_regulation (induction) of ATF4 associated with cocaine
4) Confidence 0.44 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.39 Pain Relevance 0.39
An increase in ATF4 protein occurred as early as 1 h after 100 ?
Positive_regulation (increase) of ATF4 protein
5) Confidence 0.44 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.11 Pain Relevance 0.52
This effect of cimetidine appeared to be mediated by prevention of N-oxidative metabolism of cocaine and consequent ER stress, as cimetidine also prevented the cocaine-induced increase in ATF4 (Figures 7C and S7C).
Positive_regulation (increase) of ATF4 associated with stress and cocaine
6) Confidence 0.44 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.46 Pain Relevance 0.48
M resulted in dose-dependent induction of ATF4 (Figure 6B).
Positive_regulation (induction) of ATF4
7) Confidence 0.44 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.18 Pain Relevance 0.48
The up-regulation of ATF4 has been associated with ischemia of both brain and spinal cord [49].
Positive_regulation (regulation) of ATF4 in brain associated with ischemia and spinal cord
8) Confidence 0.44 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2900267 Disease Relevance 0.43 Pain Relevance 0.19
Furthermore, ER stress-inducible genes, such as Atf4, Gadd34/Myd116, and Ddit3/CHOP, are up-regulated in the liver after high-dose methapyrilene administration.
Positive_regulation (inducible) of Atf4 in liver associated with stress
9) Confidence 0.43 Published 2007 Journal Environ Health Perspect Section Body Doc Link PMC1852695 Disease Relevance 1.19 Pain Relevance 0.10
Further, ROS generation appears to be the source of cocaine-induced ER stress, as both SKF-525A and cimetidine also completely inhibited cocaine-induced ATF4 up-regulation and cyclin A down-regulation (Figure 6F and 6G).
Positive_regulation (induced) of ATF4 associated with stress and cocaine
10) Confidence 0.32 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.18 Pain Relevance 0.69
M cocaine for 30 min is sufficient to increase endogenous ROS to a degree that activates the ATF4 signaling pathway.
Positive_regulation (activates) of ATF4 associated with cocaine
11) Confidence 0.32 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.32 Pain Relevance 0.54
, subsequently promoting translational activation of ATF4 [35,36].
Positive_regulation (activation) of ATF4
12) Confidence 0.32 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.51 Pain Relevance 0.43
We found that ATF4 was significantly up-regulated by this transient 30 min exposure to cocaine (Figure S6).
Positive_regulation (up-regulated) of ATF4 associated with cocaine
13) Confidence 0.30 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.38 Pain Relevance 0.61
M, 3 h) significantly up-regulated only ATF4 among a total of nine candidate transcription factors tested, including ATF1–4, CREB, JunB, JunD, c-Jun, and c-Fos (Figure 6A).
Positive_regulation (up-regulated) of ATF4
14) Confidence 0.30 Published 2008 Journal PLoS Medicine Section Body Doc Link PMC2504032 Disease Relevance 0.14 Pain Relevance 0.55
The up-regulation of ATF4 has been associated with ischemia of both brain and spinal cord [49].
Positive_regulation (regulation) of ATF4 in spinal cord associated with ischemia and spinal cord
15) Confidence 0.15 Published 2010 Journal BMC Genomics Section Body Doc Link PMC2900267 Disease Relevance 0.43 Pain Relevance 0.19

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