INT121589

Context Info Confidence 0.53 First Reported 2004 Last Reported 2010 Negated 0 Speculated 0 Reported most in Body Documents 10 Total Number 10 Disease Relevance 9.11 Pain Relevance 2.22

cytosol (GSK3A) carbohydrate metabolic process (GSK3A)

Anatomy Link Frequency reticulum 1 GSK3A (Homo sapiens)

Pain Link Frequency Relevance Heat Paracetamol 27 98.48 cINOD 3 75.00 tetrodotoxin 2 58.00 Analgesic 3 51.00 Ziconotide 2 46.92 Lasting pain 2 40.44 Inflammation 6 39.88 cytokine 3 25.00 metalloproteinase 5 5.00 Serotonin 4 5.00

Disease Link Frequency Relevance Heat Disease 39 100.00 Apoptosis 81 99.36 Melanoma 6 99.24 Thyroid Neoplasm 264 99.02 Stress 23 98.46 Death 44 97.16 Acquired Immune Deficiency Syndrome Or Hiv Infection 5 97.04 Colon Cancer 4 76.88 INFLAMMATION 9 75.00 Hepatocellular Cancer 6 75.00

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Key:

Protein

Mutation

Event

Anatomy

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Disease term

However, pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) delayed and decreased the extent of AAP-induced apoptosis.

Negative_regulation (inhibition) of GSK-3 associated with paracetamol and apoptosis

1) Confidence 0.53 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15665138 Disease Relevance 1.37 Pain Relevance 0.69

However, pharmacological inhibition of glycogen synthase kinase-3 (GSK-3) delayed and decreased the extent of AAP-induced apoptosis.

Negative_regulation (inhibition) of glycogen synthase kinase-3 associated with paracetamol and apoptosis

2) Confidence 0.53 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15665138 Disease Relevance 1.37 Pain Relevance 0.69

In comparison, endoplasmic reticulum stress-induced but not prooxidant-induced apoptosis of HuH7 cells was sensitive to GSK-3 inhibition.

Negative_regulation (inhibition) of GSK-3 in reticulum associated with stress and apoptosis

3) Confidence 0.53 Published 2005 Journal J. Pharmacol. Exp. Ther. Section Abstract Doc Link 15665138 Disease Relevance 1.22 Pain Relevance 0.51

Furthermore, the down-regulation of GSK-3 gene using small interference RNA resulted in a decline of the NAG-1 expression in the presence of LY294002.

Negative_regulation (down-regulation) of GSK-3 gene

4) Confidence 0.15 Published 2004 Journal J. Biol. Chem. Section Abstract Doc Link 15377673 Disease Relevance 0.49 Pain Relevance 0.20

Several small molecule inhibitors of GSK-3ß are available and demonstrate promising results both in vitro and in vivo as potential targeted therapies for the treatment of MTC.

Negative_regulation (inhibitors) of GSK-3 associated with thyroid neoplasm

5) Confidence 0.14 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.77 Pain Relevance 0

Recently, we have shown that Raf-1 activation in human MTC cells results in phosphorylation and subsequent inactivation of GSK-3ß [30]; likewise, inactivation of GSK-3ß by phosphorylation results in MTC growth inhibition both in vitro and in vivo.

Negative_regulation (inactivation) of GSK-3 associated with thyroid neoplasm

6) Confidence 0.14 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.70 Pain Relevance 0

Recently, we have shown that Raf-1 activation in human MTC cells results in phosphorylation and subsequent inactivation of GSK-3ß [30]; likewise, inactivation of GSK-3ß by phosphorylation results in MTC growth inhibition both in vitro and in vivo.

Negative_regulation (inactivation) of GSK-3 associated with thyroid neoplasm

7) Confidence 0.14 Published 2009 Journal Journal of Oncology Section Body Doc Link PMC2798103 Disease Relevance 0.75 Pain Relevance 0

In the course of screening for pharmacological inhibitors of disease-relevant protein kinases such as cyclin-dependent kinases (CDKs) [28, 29], glycogen synthase kinase-3 (GSK-3) [30], PIM1 [31], “dual-specificity, tyrosine phosphorylation regulated kinase 1A” (DYRK1A) [32–34], casein kinase 1 (CK1) [35], we discovered that several lamellarins inhibit the catalytic activity of some of these kinases.

Negative_regulation (inhibitors) of GSK-3 associated with disease

8) Confidence 0.07 Published 2008 Journal Mar Drugs Section Body Doc Link PMC2630805 Disease Relevance 0.55 Pain Relevance 0.06

In the course of screening for pharmacological inhibitors of disease-relevant protein kinases such as cyclin-dependent kinases (CDKs) [28, 29], glycogen synthase kinase-3 (GSK-3) [30], PIM1 [31], “dual-specificity, tyrosine phosphorylation regulated kinase 1A” (DYRK1A) [32–34], casein kinase 1 (CK1) [35], we discovered that several lamellarins inhibit the catalytic activity of some of these kinases.

Negative_regulation (inhibitors) of glycogen synthase kinase-3 associated with disease

9) Confidence 0.07 Published 2008 Journal Mar Drugs Section Body Doc Link PMC2630805 Disease Relevance 0.55 Pain Relevance 0.06

In addition, pigmented cells accumulated a large amount of glycogen in their cytoplasm which might be associated with inhibition of GSK3, which in case of melanoma has been linked to different modes of cell death.

Negative_regulation (inhibition) of GSK3 associated with melanoma and death

10) Confidence 0.01 Published 2010 Journal International Journal of Molecular Sciences Section Body Doc Link PMC2852855 Disease Relevance 1.34 Pain Relevance 0

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