INT246776

From wiki-pain
Jump to: navigation, search
Context Info
Confidence 0.48
First Reported 2008
Last Reported 2009
Negated 0
Speculated 0
Reported most in Body
Documents 18
Total Number 18
Disease Relevance 6.82
Pain Relevance 0.12

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

cytosol (Tsc2) signal transduction (Tsc2) Golgi apparatus (Tsc2)
nucleus (Tsc2) intracellular (Tsc2) protein complex (Tsc2)
Anatomy Link Frequency
muscle 1
germline 1
epithelial cells 1
reticulum 1
Tsc2 (Rattus norvegicus)
Pain Link Frequency Relevance Heat
agonist 11 99.82 Very High Very High Very High
Paracetamol 60 72.52 Quite High
Angina 6 14.16 Low Low
anesthesia 11 7.60 Low Low
cerebral cortex 6 5.00 Very Low Very Low Very Low
transdermal 6 5.00 Very Low Very Low Very Low
adenocard 6 5.00 Very Low Very Low Very Low
cytokine 1 5.00 Very Low Very Low Very Low
Disease Link Frequency Relevance Heat
Tuberous Sclerosis 67 100.00 Very High Very High Very High
Sprains And Strains 18 99.58 Very High Very High Very High
Hyperglycemia 70 99.16 Very High Very High Very High
Diabetes Mellitus 429 99.02 Very High Very High Very High
Cancer 131 98.64 Very High Very High Very High
Hamartoma 48 98.58 Very High Very High Very High
Anaplastic Astrocytoma 36 98.54 Very High Very High Very High
Renal Cancer 18 98.00 Very High Very High Very High
Stress 89 96.96 Very High Very High Very High
Adhesions 11 92.12 High High

Sentences Mentioned In

Key: Protein Mutation Event Anatomy Negation Speculation Pain term Disease term
Likely, patients with a deletion that disrupts the PKD1 and TSC2 genes are usually identified as TSC patients.
Negative_regulation (disrupts) of TSC2
1) Confidence 0.48 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691673 Disease Relevance 0.61 Pain Relevance 0
Ozcan et al. [98] found that loss of TSC1 or TSC2 in cell lines and mouse or human tumours caused endoplasmic reticulum (ER) stress and activated the unfolded protein response.
Negative_regulation (loss) of TSC2 in reticulum associated with stress and cancer
2) Confidence 0.35 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691673 Disease Relevance 0.54 Pain Relevance 0
First described in the 1950s, the Eker rat strain contains a germline inactivation of one allele of the gene encoding TSC2 and has served as an animal model for hereditary renal cell carcinoma [100, 101].
Negative_regulation (inactivation) of TSC2 in germline associated with renal cancer and sprains and strains
3) Confidence 0.35 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691673 Disease Relevance 0.76 Pain Relevance 0
On the other hand, recent evidence suggests that both tuber giant cells and SEGA cells have similar immunophenotypes, and SEGAs commonly sustain two-hit inactivation of either TSC1 or TSC2.
Negative_regulation (inactivation) of TSC2 associated with anaplastic astrocytoma
4) Confidence 0.35 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691673 Disease Relevance 0.40 Pain Relevance 0
Inhibition of the GAP function of TSC2 shifts the balance of its substrate Rheb to the Rheb-GTP form, which activates the mTOR protein and ultimately leads to phosphorylation of ribosomal protein S6 and 4E-BP1 resulting in increased protein synthesis and cell proliferation.
Negative_regulation (Inhibition) of TSC2
5) Confidence 0.35 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691673 Disease Relevance 0.24 Pain Relevance 0
For many years, the prevailing model has been that the hamartomas of TSC develop through a two-hit mechanism in which there is complete loss of expression of functional TSC1 or TSC2, supported by findings of loss of heterozygosity (LOH) in TSC tumour samples [23-26].
Negative_regulation (loss) of TSC2 associated with cancer and hamartoma
6) Confidence 0.35 Published 2008 Journal Current Genomics Section Body Doc Link PMC2691673 Disease Relevance 0.44 Pain Relevance 0
Interestingly, these data do not appear to predict down-stream Akt signaling since the phosphorylation level of mTOR (Ser2448) [9] (Figure 2A), tuberous sclerosis complex-2 (TSC2) and forkhead box O1 (FoxO1) (data not shown) was lower in the very aged muscle.
Negative_regulation (level) of TSC2 in muscle associated with tuberous sclerosis
7) Confidence 0.30 Published 2009 Journal PLoS ONE Section Body Doc Link PMC2712760 Disease Relevance 0.43 Pain Relevance 0.07
Activation of phosphatidylinositol 3-kinase (PI 3-kinase) and phosphorylation of serine/threonine kinase Akt/protein kinase B (PKB) by certain agonists lead to inactivation of tuberin (25–28).
Negative_regulation (inactivation) of tuberin associated with agonist
8) Confidence 0.22 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.47 Pain Relevance 0.05
CONCLUSIONS—Hyperglycemia in type 1 diabetes and treatment of proximal tubular epithelial cells with high glucose leads to phosphorylation/inactivation of tuberin and downregulation of OGG1 via a redox-dependent activation of Akt in renal tubular epithelial cells.
Negative_regulation (phosphorylation/inactivation) of tuberin in epithelial cells associated with hyperglycemia and diabetes mellitus
9) Confidence 0.18 Published 2008 Journal Diabetes Section Abstract Doc Link PMC2551671 Disease Relevance 0.38 Pain Relevance 0
Phosphorylation of tuberin by Akt affects its function through at least two mechanisms: first, phosphorylation decreases the activity of tuberin; second, phosphorylation destabilizes tuberin by disrupting the complex formation between hamartin and tuberin, resulting in ubiquitination of free tuberin and its degradation by the proteosome (27).
Negative_regulation (decreases) of tuberin
10) Confidence 0.18 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.12 Pain Relevance 0
In this study, we provide evidence that diabetes is associated with enhanced phosphorylation and inactivation of tuberin via the redox-dependent activation of Akt.
Negative_regulation (inactivation) of tuberin associated with diabetes mellitus
11) Confidence 0.18 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.49 Pain Relevance 0
Therefore, tuberin deficiency, through its phosphorylation, is upstream of OGG1 in the pathway linking high glucose to DNA damage.
Negative_regulation (deficiency) of tuberin
12) Confidence 0.18 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.22 Pain Relevance 0
These data show that MCT cells are a relevant model and confirm that phosphorylation and inactivation of tuberin via the redox-dependent activation of Akt play a major role in OGG1 downregulation and 8-oxodG accumulation.
Negative_regulation (inactivation) of tuberin
13) Confidence 0.18 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.39 Pain Relevance 0
In summary, our data provide the first evidence that hyperglycemia and high glucose lead to phosphorylation/inactivation of tuberin and downregulation of DNA repair enzyme OGG1 via the redox-dependent activation of Akt (Fig. 9).
Negative_regulation (inactivation) of tuberin associated with hyperglycemia
14) Confidence 0.18 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.56 Pain Relevance 0
Partial deficiency in tuberin causes a decrease in OGG1 expression, suggesting that OGG1 is downstream of tuberin (20).
Negative_regulation (deficiency) of tuberin
15) Confidence 0.16 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0.76 Pain Relevance 0
Next, we assessed whether ROS generation mediates the effect of high glucose–induced Akt and tuberin phosphorylation and OGG1 downregulation in MCT cells.
Negative_regulation (downregulation) of tuberin
16) Confidence 0.08 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0 Pain Relevance 0
ROS are required for high glucose–induced Akt and tuberin phosphorylation and OGG1 downregulation in MCT cells.
Negative_regulation (downregulation) of tuberin
17) Confidence 0.08 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0 Pain Relevance 0
The correlation between high glucose–induced Akt and tuberin phosphorylation and OGG1 downregulation led us to test the hypothesis that the PI 3-kinase/Akt pathway activated by glucose results in tuberin phosphorylation and OGG1 downregulation.
Negative_regulation (downregulation) of tuberin
18) Confidence 0.08 Published 2008 Journal Diabetes Section Body Doc Link PMC2551671 Disease Relevance 0 Pain Relevance 0

General Comments

This test has worked.

Personal tools
Namespaces

Variants
Actions
Navigation
Toolbox