INT75497

Context Info Confidence 0.61 First Reported 1997 Last Reported 2010 Negated 3 Speculated 3 Reported most in Body Documents 28 Total Number 31 Disease Relevance 11.04 Pain Relevance 7.09

cytosol (JUN) nucleoplasm (JUN) nuclear chromosome (JUN) aging (JUN) nucleus (JUN) DNA binding (JUN)

Anatomy Link Frequency T cells 2 lymph node 1 U373 MG 1 neuronal 1 neuroendocrine cells 1 JUN (Homo sapiens)

Pain Link Frequency Relevance Heat Inflammation 181 100.00 cytokine 110 100.00 Glutamate receptor 6 99.98 Enkephalin 15 99.90 COX2 2 99.80 metalloproteinase 217 99.76 local anesthetic 3 99.74 antidepressant 7 99.60 dexamethasone 19 99.26 cINOD 30 98.92

Disease Link Frequency Relevance Heat INFLAMMATION 220 100.00 Adhesions 18 100.00 Stress 64 99.48 Neuroblastoma 5 99.48 Hyperplasia 3 99.20 Metastasis 21 99.18 Necrosis 23 99.12 Glioma 3 99.12 Cancer 180 98.94 Apoptosis 261 98.86

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

After 1 h or 96 h of treatment, Fos and Jun protein levels were altered and the DNA-binding activity of AP-1 was increased in response to both substances.

Regulation (altered) of Jun

1) Confidence 0.61 Published 2005 Journal Neuropharmacology Section Abstract Doc Link 15814102 Disease Relevance 0.08 Pain Relevance 0.35

This effect was specific, as the activity of nuclear factor kappabeta, nuclear factor of activated T cells, and specific protein-1 was not altered and several other volatile anesthetics studied did not affect AP-1 activation.

Neg (not) Regulation (affect) of AP-1 in T cells

2) Confidence 0.45 Published 2004 Journal Anesthesiology Section Body Doc Link 15329596 Disease Relevance 0 Pain Relevance 0

Neurotoxicity of lidocaine involves specific activation of the p38 mitogen-activated protein kinase, but not extracellular signal-regulated or c-jun N-terminal kinases, and is mediated by arachidonic acid metabolites.

Neg (not) Regulation (signal-regulated) of c-jun associated with drug induced neurotoxicity and lidocaine

3) Confidence 0.44 Published 2006 Journal Anesthesiology Section Title Doc Link 17065898 Disease Relevance 0.37 Pain Relevance 0.40

Osmotic and glutamate receptor regulation of c-Jun NH(2)-terminal protein kinase in neuroendocrine cells.

Regulation (regulation) of c-Jun in neuroendocrine cells associated with glutamate receptor

4) Confidence 0.44 Published 2000 Journal Am. J. Physiol. Endocrinol. Metab. Section Title Doc Link 10950813 Disease Relevance 0.18 Pain Relevance 0.30

We report that in human colorectal carcinoma cells NSAIDs stimulated the three families of MAPK, extracellular regulated kinases, c-Jun N-terminal kinases, p38 MAPK and that this stimulation is prevented by N-acetyl cysteine.

Regulation (regulated) of c-Jun associated with colon cancer and cinod

5) Confidence 0.44 Published 2002 Journal Biochem. Pharmacol. Section Abstract Doc Link 11841790 Disease Relevance 0.36 Pain Relevance 0.65

Furthermore, c-Jun immunoreactivity was also observed in disc cell clusters, thus demonstrating them to be active transcriptional sites in disc tissue. c-Fos immunoreactivity was seen in 15/38 and c-Jun in 28/38 herniated discs (39% and 74% respectively).

Regulation (immunoreactivity) of c-Jun associated with intervertebral disk displacement

6) Confidence 0.27 Published 2002 Journal Eur Spine J Section Abstract Doc Link 12384753 Disease Relevance 0.17 Pain Relevance 0.03

In order to approach the astroglial implication of addictive and neurotoxic processes associated with psychostimulant drug abuse, the effects of amphetamine or cocaine (1-100 microM) on redox status, AP-1 transcription factor and pro-enkephalin, an AP-1 target gene, were investigated in the human astrocyte-like U373 MG cells.

Regulation (target) of AP-1 in U373 MG associated with drug abuse, enkephalin and cocaine

7) Confidence 0.27 Published 2005 Journal Neuropharmacology Section Abstract Doc Link 15814102 Disease Relevance 0.10 Pain Relevance 0.30

Because astrocytes interact extensively with the neurons in the brain, our data led us to conclude that oxidation-regulated AP-1 target genes may represent one of the molecular mechanisms underlying neuronal adaptation associated with psychostimulant dependence.

Regulation (regulated) of AP-1 in neuronal associated with addiction

8) Confidence 0.27 Published 2005 Journal Neuropharmacology Section Abstract Doc Link 15814102 Disease Relevance 0.06 Pain Relevance 0.38

BACKGROUND: To explore whether cytotoxicity of local anesthetics is related to apoptosis, the authors examined how local anesthetics affect mitogen-activated protein kinase (MAPK) family members, extracellular signal-regulated kinases (ERKs), c-Jun N-terminal kinases (JNKs)-stress-activated protein kinases, and p38 kinase, which are known to play important roles in apoptosis.

Spec (examined) Regulation (affect) of c-Jun associated with stress, apoptosis and local anesthetic

9) Confidence 0.26 Published 2002 Journal Anesthesiology Section Abstract Doc Link 11981161 Disease Relevance 0.37 Pain Relevance 0.20

Transcription factors are also regulated by S-glutathionylation in response to ROS, including p53, AP-1, c-Jun, and NF-kappa B [36].

Regulation (regulated) of c-Jun

10) Confidence 0.26 Published 2010 Journal Biol Trace Elem Res Section Body Doc Link PMC2855032 Disease Relevance 0.18 Pain Relevance 0.04

NFAT, C/EBP, Jun and AP-1 transcription factor regulation of LTR activity also have distinct differences in monocyte-macrophages compared to T cells.

Regulation (regulation) of Jun in T cells

11) Confidence 0.24 Published 2009 Journal Retrovirology Section Body Doc Link PMC2805609 Disease Relevance 0.23 Pain Relevance 0

Other up-regulated genes at this time point were the transcription factor Jun and BTG1.

Regulation (regulated) of Jun

12) Confidence 0.23 Published 2005 Journal BMC Cancer Section Body Doc Link PMC1182358 Disease Relevance 0.54 Pain Relevance 0.03

Moreover, c-jun and junD activity were affected by glucosamine pretreatment in HPCs.

Regulation (affected) of c-jun

13) Confidence 0.20 Published 2007 Journal Arthritis Res Ther Section Body Doc Link PMC2212570 Disease Relevance 0.30 Pain Relevance 0.15

There is substantial evidence indicating that mitogen-activated protein kinase (MAPK), a family including extracellular signal-regulated protein kinase, p38 MAPK, and c-Jun N-terminal kinase, can be activated by chronic morphine treatment in the central and peripheral nervous systems and that application of a MAPK inhibitor reduces morphine tolerance and dependence.

Regulation (regulated) of c-Jun in peripheral nervous systems associated with addiction, tolerance and morphine

14) Confidence 0.19 Published 2009 Journal Mol. Neurobiol. Section Abstract Doc Link 19468867 Disease Relevance 0 Pain Relevance 0.86

A triple function of PLA2-derived lipid mediators has been suggested: causing immediate inflammatory signs, involvement in secondary processes, e.g., superoxide free radical (O2) generation, apoptosis, or tumour necrosis factor-alpha (TNF-alpha)-cytotoxicity, and controlling the expression and activation of pivotal proteins implicated in inflammation and cell development, e.g., cytokines, adhesion proteins, proteinases, NF-kappaB, fos/jun/AP-1, c-Myc, or p21ras.

Regulation (controlling) of jun associated with necrosis, inflammation, cancer, apoptosis, adhesions and cytokine

15) Confidence 0.19 Published 1997 Journal Expert Opin Investig Drugs Section Abstract Doc Link 15989628 Disease Relevance 0.84 Pain Relevance 0.31

The MEK (MAP kinase kinase) and extracellular signal regulated kinases (ERK) pathway primarily responds to cellular proliferation signals, while the p38 MAP kinases and c-Jun N-terminal kinases are modulated by cytokines, growth factors and a variety of cellular stress signals [97].

Regulation (modulated) of c-Jun associated with stress, hyperplasia and cytokine

16) Confidence 0.19 Published 2003 Journal Comp Hepatol Section Body Doc Link PMC151270 Disease Relevance 0.27 Pain Relevance 0.16

As with the network findings from the entire population of newborns, the networks identified here integrate proteins known to be involved in cell cycle regulation including JUN, as well as stress-response proteins such as interleukin-8 (IL-8), the pro-inflammatory interleukin 1 family member IL1-?

Regulation (regulation) of JUN associated with stress and inflammation

17) Confidence 0.18 Published 2007 Journal PLoS Genetics Section Body Doc Link PMC2082467 Disease Relevance 0.34 Pain Relevance 0.05

Therefore, we examined whether these cytokines affected MMP-12 secretion mediated through regulation of c-Jun activity in ASMC.

Spec (whether) Regulation (regulation) of Jun associated with metalloproteinase and cytokine

18) Confidence 0.18 Published 2005 Journal Respir Res Section Body Doc Link PMC1363355 Disease Relevance 0.07 Pain Relevance 0.70

Hypoxia can promote lymph node metastasis via up-regulation of PLAUR [39], and up-regulation of HIF1a, JUN and PLAUR in our invasive cell lines hints at possible activation of JUN/AP1 and HIF/ARNT pathways in melanoma (Figure 5).

Regulation (regulation) of JUN in lymph node associated with melanoma, hypoxia and metastasis

19) Confidence 0.17 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2794539 Disease Relevance 1.63 Pain Relevance 0

The accumulation of cells in G1 was associated with decreased levels of expression of cyclin D1 but no effect was seen on the expression of CDK4 or the immediate early response gene c-jun.

Neg (no) Regulation (effect) of c-jun

20) Confidence 0.14 Published 1998 Journal Breast Cancer Res. Treat. Section Abstract Doc Link 9598866 Disease Relevance 0.86 Pain Relevance 0.08

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