INT139252

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Context Info
Confidence 0.52
First Reported 2006
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 15
Total Number 16
Disease Relevance 0.91
Pain Relevance 4.24

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

signal transduction (Per2) nucleus (Per2) protein binding transcription factor activity (Per2)
cytoplasm (Per2) signal transducer activity (Per2)
Anatomy Link Frequency
retina 2
photoreceptors 1
inner nuclear layer 1
fibroblasts 1
hippocampus 1
Per2 (Mus musculus)
Pain Link Frequency Relevance Heat
GABAergic 117 99.98 Very High Very High Very High
gABA 1161 99.92 Very High Very High Very High
agonist 252 99.48 Very High Very High Very High
Hippocampus 5 95.12 Very High Very High Very High
GABA receptor 81 91.72 High High
Dopamine 675 84.44 Quite High
Glutamate 117 84.08 Quite High
antagonist 253 82.40 Quite High
Action potential 117 81.84 Quite High
imagery 55 69.40 Quite High
Disease Link Frequency Relevance Heat
Neurodegenerative Disease 35 96.52 Very High Very High Very High
Ganglion Cysts 234 96.28 Very High Very High Very High
Cognitive Disorder 10 93.28 High High
Stress 7 81.40 Quite High
Sleep Disorders 99 50.00 Quite Low
Targeted Disruption 37 50.00 Quite Low
Atherosclerosis 22 50.00 Quite Low
Disorder Of Lipid Metabolism 15 50.00 Quite Low
Hyperlipidemia 15 50.00 Quite Low
Manic Depressive Disorder 7 50.00 Quite Low

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
The loss of Per1 alone does not abolish rhythmicity, but the loss of Per2 alone leads to a slowly decaying amplitude of the oscillation [18].
Negative_regulation (loss) of Per2
1) Confidence 0.52 Published 2007 Journal PLoS Computational Biology Section Body Doc Link PMC2134962 Disease Relevance 0 Pain Relevance 0
Per2 mRNA level was decreased at CT0 and CT4 in apoE-/-mice, in contrast, which was increased at CT12 and CT16, compared to C57BL/6J mice (Fig. 4).
Negative_regulation (decreased) of Per2
2) Confidence 0.48 Published 2009 Journal Lipids Health Dis Section Body Doc Link PMC2807425 Disease Relevance 0 Pain Relevance 0
For example, multiple processes that reduce the half-life of Per2 mRNA all produce a shortened period.
Negative_regulation (reduce) of Per2
3) Confidence 0.38 Published 2007 Journal PLoS Computational Biology Section Body Doc Link PMC2134962 Disease Relevance 0 Pain Relevance 0
Localization of rhythmic PER2::LUC expression to the inner nuclear layer is consistent with the persistence of PER2::LUC rhythms in photoreceptor-degenerate mouse retinas [43], and with the persistence of Per2 rhythms in photoreceptor-degenerate RCS retinas [63].
Negative_regulation (persistence) of PER2 in inner nuclear layer
4) Confidence 0.37 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0.07 Pain Relevance 0.12
Light pulses beginning in the early retinal subjective night (CT 13) phase delayed retinal PER2::LUC rhythms by approximately 2.3 h, whereas light pulses beginning in the late retinal subjective night (CT 19.5) induced phase advances of approximately 1.5 h (Figure 6A–6C).
Negative_regulation (delayed) of PER2
5) Confidence 0.37 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0 Pain Relevance 0.18
Therefore, GABA-induced inhibition of ensemble PER2::LUC rhythms is retina specific.


Negative_regulation (inhibition) of PER2 in retina associated with gaba
6) Confidence 0.37 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0 Pain Relevance 0.81
At 2 mM or 3 mM, GABA further inhibited PER2::LUC luminescence levels and resulted in rapid damping of PER2::LUC rhythms (Figure 7C and 7D).
Negative_regulation (inhibited) of PER2 associated with gaba
7) Confidence 0.37 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0 Pain Relevance 0.58
To further test whether GABAergic suppression of PER2::LUC luminescence rhythms results from an effect on the core function of the retinal clock, we tested whether prolonged application of GABA can halt the molecular oscillation of the retinal clock.
Spec (whether) Negative_regulation (suppression) of PER2 associated with gaba and gabaergic
8) Confidence 0.37 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0 Pain Relevance 0.48
In contrast, if the observed suppression of PER2::LUC luminescence rhythms during GABA application did not have an effect on the core clock, but merely on luminescence output, then the phase of restored rhythms should be predicted by the projected phase of the baseline rhythm obtained prior to treatment.
Negative_regulation (suppression) of PER2 associated with gaba
9) Confidence 0.37 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0 Pain Relevance 0.41
Rat-1 fibroblasts treated with glucose have been shown to exhibit clock resetting by the down-regulation of Per1 and Per2 [17].
Negative_regulation (regulation) of Per2 in fibroblasts
10) Confidence 0.34 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2734168 Disease Relevance 0 Pain Relevance 0
Therefore, the substantial reduction in PER2::LUC expression upon GABA treatment is likely due to posttranscriptional regulation.
Negative_regulation (reduction) of PER2 associated with gaba
11) Confidence 0.32 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0 Pain Relevance 0.54
Convincing evidence for the presence of GABAC receptors on rod photoreceptors and horizontal, amacrine, and ganglion cells in the mammalian retina is still lacking; however, GABAA receptors may mediate the action of GABA on these cell types, because the GABAA receptor agonist muscimol alone partially reduced rhythmic PER2::LUC amplitudes (Figure S3A), and GABAA receptors have been detected in these retinal cell types [31].


Negative_regulation (reduced) of PER2 in photoreceptors associated with ganglion cysts, gaba and agonist
12) Confidence 0.32 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0.10 Pain Relevance 0.43
However, the ability of exogenous GABA to suppress substantially PER2::LUC rhythms is unique to the retina, as similar experiments with SCN slices do not yield similar results.
Negative_regulation (suppress) of PER2 in retina associated with gaba
13) Confidence 0.32 Published 2008 Journal PLoS Biology Section Body Doc Link PMC2567003 Disease Relevance 0.07 Pain Relevance 0.59
and Bmal1, 30 cycles for mCry1, and 34 cycles for mPer2.
Negative_regulation (cycles) of mPer2
14) Confidence 0.18 Published 2007 Journal J Circadian Rhythms Section Body Doc Link PMC1803776 Disease Relevance 0 Pain Relevance 0
And PERIOD proteins were decreased by 57.5%.
Negative_regulation (decreased) of PERIOD
15) Confidence 0.06 Published 2006 Journal Sichuan Da Xue Xue Bao Yi Xue Ban Section Body Doc Link 17037739 Disease Relevance 0 Pain Relevance 0
Alternatively, circadian disruption may impact brain function more directly, as mice lacking one of the core clock genes, Period2, that drives circadian rhythms at the cellular level, exhibit alterations in neural/progenitor cell proliferation in the hippocampus [40].
Negative_regulation (lacking) of Period2 in hippocampus associated with hippocampus
16) Confidence 0.01 Published 2010 Journal PLoS ONE Section Body Doc Link PMC2995744 Disease Relevance 0.67 Pain Relevance 0.11

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