INT187504

Context Info Confidence 0.65 First Reported 2005 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 5 Total Number 11 Disease Relevance 1.30 Pain Relevance 0.22

nucleoplasm (Prkaa2) nucleus (Prkaa2) protein binding, bridging (Prkaa2) protein complex (Prkaa2) response to stress (Prkaa2) cytoplasm (Prkaa2)

Anatomy Link Frequency hypothalamus 1 Prkaa2 (Rattus norvegicus) Prkaa2 - R531G (2)

Pain Link Frequency Relevance Heat Intracerebroventricular 15 97.44 Inflammatory response 7 94.28 cytokine 54 72.08 agonist 3 70.88 Inflammatory mediators 11 50.00 Inflammation 34 7.80 imagery 14 5.00 qutenza 7 5.00 Kinase C 7 5.00 anesthesia 6 5.00

Disease Link Frequency Relevance Heat Aging 3 95.68 Stress 168 94.56 INFLAMMATION 53 93.88 Obesity 117 92.96 Immunization 7 85.44 Diabetes Mellitus 7 82.08 Appetite Loss 42 60.76 Body Weight 15 18.32 Disease 36 5.00 Alzheimer's Dementia 15 5.00

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Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

Inside the cell (in vivo) AICAR is converted to ZMP (an analog of AMP) which activates AMP kinase kinase (AMPKK) which in turn activates AMP kinase (AMPK) by phosphorylation on residues Thr 172 of the ?

Gene_expression (kinase) of AMPK

1) Confidence 0.65 Published 2005 Journal J Neuroinflammation Section Body Doc Link PMC1262754 Disease Relevance 0.09 Pain Relevance 0.11

AMPK, ACC, p70S6K and 4EBP1 protein expression (Figures 4b–e, lower panels).

Gene_expression (expression) of AMPK

2) Confidence 0.51 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0 Pain Relevance 0.07

In addition, we did not observe any normal stimulation of AMPK activity by AICAR in the hypothalamus of exercised rats, indicating that AMPK pathway is disrupted.

Gene_expression (pathway) of AMPK in hypothalamus

3) Confidence 0.44 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0.30 Pain Relevance 0

Consistent with food intake, AICAR increased AMPK threonine and ACC serine phosphorylation levels in the hypothalami of control rats, whilst in exercised animals, AICAR did not change AMPK/ACC phosphorylation status (Figures 3b and c).

Gene_expression (threonine) of AMPK

4) Confidence 0.39 Published 2008 Journal PLoS ONE Section Body Doc Link PMC2585815 Disease Relevance 0 Pain Relevance 0.04

An important subsidiary finding of our study was that, although the expression levels of the WT and R531G mutants of AMPK in the stably transfected cells were identical, the RG mutant was about twice as active when measured in the absence of AMP, associated with a 2-fold higher basal Thr-172 phosphorylation (Figure 1).

Gene_expression (expression) of AMPK (R531G)

5) Confidence 0.22 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0.23 Pain Relevance 0

We generated isogenic cell lines stably expressing AMPK complexes containing AMP-sensitive (wild-type, WT) or AMP-insensitive (R531G) ?

Gene_expression (expressing) of AMPK

6) Confidence 0.20 Published 2010 Journal Cell Metabolism Section Abstract Doc Link PMC2935965 Disease Relevance 0.05 Pain Relevance 0

Antibodies against AMPK-?

Gene_expression (Antibodies) of AMPK

7) Confidence 0.19 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0.13 Pain Relevance 0

Antibodies against AMPK-?

Gene_expression (Antibodies) of AMPK

8) Confidence 0.19 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0.13 Pain Relevance 0

Effects of Other AMPK-Activating Drugs

Gene_expression (Effects) of AMPK

9) Confidence 0.19 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0.22 Pain Relevance 0

Antibodies against AMPK-?

Gene_expression (Antibodies) of AMPK

10) Confidence 0.19 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0.14 Pain Relevance 0

After transfection, Flp-In HEK293 cells stably expressing either WT or R531G AMPK-?

Gene_expression (expressing) of AMPK (R531G)

11) Confidence 0.19 Published 2010 Journal Cell Metabolism Section Body Doc Link PMC2935965 Disease Relevance 0 Pain Relevance 0

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