INT289580

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Context Info
Confidence 0.58
First Reported 2009
Last Reported 2010
Negated 0
Speculated 1
Reported most in Body
Documents 23
Total Number 24
Disease Relevance 9.03
Pain Relevance 0.48

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

nucleoplasm (Sirt1) nuclear envelope (Sirt1) histone binding (Sirt1)
nucleolus (Sirt1) nucleus (Sirt1) enzyme binding (Sirt1)
Anatomy Link Frequency
plasma 3
hypothalamus 1
thyroid 1
fat 1
body 1
Sirt1 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
antagonist 115 99.12 Very High Very High Very High
Central nervous system 23 96.56 Very High Very High Very High
Hippocampus 23 81.04 Quite High
addiction 23 80.32 Quite High
Inflammation 3 40.80 Quite Low
fibrosis 14 6.24 Low Low
anesthesia 49 5.00 Very Low Very Low Very Low
imagery 2 5.00 Very Low Very Low Very Low
ketamine 1 5.00 Very Low Very Low Very Low
Perioperative pain 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Aids-related Complex 506 100.00 Very High Very High Very High
Body Weight 391 100.00 Very High Very High Very High
Appetite Loss 115 99.78 Very High Very High Very High
Myocardial Infarction 78 98.92 Very High Very High Very High
Apoptosis 63 96.36 Very High Very High Very High
Hypertrophy 14 95.52 Very High Very High Very High
Stress 31 93.92 High High
Repression 23 93.08 High High
Obesity 116 87.68 High High
Hyperphagia 23 87.44 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
This compound (EX-527) is a small, selective inhibitor of SIRT1 that does not inhibit histone deacetylases and is specific for Sirt1 over other sirtuin family members [16], [17].
Negative_regulation (inhibitor) of SIRT1
1) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.56 Pain Relevance 0
Blocking the melanocortin receptors with the melanocortin antagonist SHU9119 attenuated the anorectic effect of Sirt1 inhibition.
Negative_regulation (inhibition) of Sirt1 associated with appetite loss and antagonist
2) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.45 Pain Relevance 0.09
Blocking hypothalamic Sirt1 activity (Figure S4B) reversed the decrease in FoxO1 acetylation, suggesting that fasting induced deacetylation of FoxO1 required Sirt1 (Figure 4B).
Negative_regulation (Blocking) of Sirt1
3) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.18 Pain Relevance 0
As shown in Figure 1D, inhibition of hypothalamic Sirt1 resulted in a significant rise in plasma T3 and T4 levels, strongly suggesting that the melanocortin system was positively activated when Sirt1 activity was inhibited.


Negative_regulation (inhibited) of Sirt1 in plasma
4) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.35 Pain Relevance 0
Rats with diminished ARC Sirt1 protein consumed less food (Figure 1B, left), and gained less weight compared to the control group (Figure 1B, right).


Negative_regulation (diminished) of Sirt1 associated with aids-related complex
5) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.49 Pain Relevance 0.03
Under our experimental conditions we could not detect any significant change in the acetylation of ARC Stat3 by fasting, inhibition of Sirt1, or leptin administration, working against the hypothesis that Sirt1 targets Stat3 in the hypothalamus.
Negative_regulation (inhibition) of Sirt1 in hypothalamus associated with aids-related complex
6) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.25 Pain Relevance 0.03
Since hypothalamic Sirt1 regulates food intake through melanocortin receptors (Figure 1C), we investigated the effect of inhibition of hypothalamic Sirt1 in POMC and AgRP expression.
Spec (investigated) Negative_regulation (inhibition) of Sirt1
7) Confidence 0.58 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.29 Pain Relevance 0
As shown in Figure 1D, inhibition of hypothalamic Sirt1 resulted in a significant rise in plasma T3 and T4 levels, strongly suggesting that the melanocortin system was positively activated when Sirt1 activity was inhibited.


Negative_regulation (inhibition) of Sirt1 in plasma
8) Confidence 0.50 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.30 Pain Relevance 0
Inhibition of hypothalamic Sirt1 resulted in decreased binding of FoxO1 (Figure 4C).
Negative_regulation (Inhibition) of Sirt1
9) Confidence 0.50 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.14 Pain Relevance 0
Third, inhibition of hypothalamic Sirt1 resulted in increased levels of serum thyroid hormones, which are strong stimulators of basic metabolic rate and thermogenesis.
Negative_regulation (inhibition) of Sirt1 in thyroid
10) Confidence 0.50 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.44 Pain Relevance 0.04
Since the inhibition of hypothalamic Sirt1 induced an anorectic effect in a SHU9119 dependent manner, we measured the T3 and T4 plasma levels of EX527 infused animals.
Negative_regulation (inhibition) of Sirt1 in plasma associated with appetite loss
11) Confidence 0.50 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.41 Pain Relevance 0.03
Fasting induced decrease in p53 acetylation [10] was also reversed by inhibition of Sirt1 function, and Stat3 acetylation was insensitive to Sirt1 inhibition (data not shown).
Negative_regulation (inhibition) of Sirt1
12) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.16 Pain Relevance 0
To block Sirt1 enzymatic activity we used a potent Sirt1 inhibitor [15].
Negative_regulation (inhibitor) of Sirt1
13) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.51 Pain Relevance 0
In addition, hypothalamic Sirt1 showed to regulate S6K signaling such that inhibition of the fasting induced Sirt1 activity results in up-regulation of the S6K pathway.
Negative_regulation (inhibition) of Sirt1
14) Confidence 0.43 Published 2009 Journal PLoS ONE Section Abstract Doc Link PMC2790615 Disease Relevance 0.46 Pain Relevance 0.04
As shown in Figure 5C (Figure S5 bottom panels), inhibition of the hypothalamic Sirt1 activity reversed the fasting-induced decrease in S6K signaling.


Negative_regulation (inhibition) of Sirt1
15) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.37 Pain Relevance 0
For example, in the liver, the Sirt1 protein level increases upon fasting [3] and decreases by high fat diet [4].
Negative_regulation (decreases) of Sirt1 in fat
16) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.45 Pain Relevance 0.09
Inhibition of hypothalamic Sirt1 activity reversed the fasting induced decrease of FoxO1 acetylation, and resulted in increased POMC and decreased AgRP expressions.
Negative_regulation (Inhibition) of Sirt1
17) Confidence 0.43 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.45 Pain Relevance 0.09
To block Sirt1 enzymatic activity we used a potent Sirt1 inhibitor [15].
Negative_regulation (block) of Sirt1
18) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.52 Pain Relevance 0
Fasting induced down-regulation of hypothalamic S6K signaling is reversed by leptin as well as by inhibition of Sirt1.
Negative_regulation (inhibition) of Sirt1
19) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.05 Pain Relevance 0
Fasting induced decrease in p53 acetylation [10] was also reversed by inhibition of Sirt1 function, and Stat3 acetylation was insensitive to Sirt1 inhibition (data not shown).
Negative_regulation (inhibition) of Sirt1
20) Confidence 0.42 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2790615 Disease Relevance 0.16 Pain Relevance 0

General Comments

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