Dear Professor and colleagues:
inflammation and cell proliferation induced via activation of nFKappaB leading to an increase in the transcription of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6...)
in case of abnormal metabolism, cancer cells need inflammation to growth and to form a new blood vessels "neoangiogenesis" which will supply cancer cells by nutrients and oxygen... thus, to the spread of tumors to other organs which we call "Metastasis".
In the other hand, Sugar supports this mechanism, but how? I mean what are the specific signaling pathways that lead to increasing Glucose metabolism during aerobic glycosis (Warburg effect)!!!??
Could anybody help me to know what are the most signaling pathways involved in the metabolic pathways...
Thank you very much for you valuable answers,
Sincerely,
Fouzia
Hi,
This might help (Article GSK3 and its interactions with the PI3K/AKT/mTOR signalling network
). I would consider mTOR signalling as it regulates glucose metabolism.Regards,
J-P
Mitochondrial GSK-3 (mGSK-3) contributes to the regulation of energy metabolism: it down-modulates both the Krebs cycle, by inactivating pyruvate dehydrogenase, and oxidative phosphorylation, by inhibiting NADH:ubiquinone oxidoreductase, i.e., respiratory chain (RC) complex I .
[Reference]
Hoshi M., Takashima A., Noguchi K., Murayama M., Sato M., Kondo S., et al. (1996). Regulation of mitochondrial pyruvate dehydrogenase activity by tau protein kinase I/glycogen synthase kinase 3beta in brain. Proc. Natl. Acad. Sci. U.S.A. 93 2719–2723.
GSK3beta is negatively downregulated signalling moleculue. That means, when GSK3beta is phosphorylated at serine 9 in presence of signals like Akt/PI3K/PKA/Wnt , they participate in metabolic syndromes.
As you have mention' GSK3beta induces inflammation and cell proliferation via activation of nFKappaB leading to an increase in the transcription of pro-inflammatory cytokines (IL-1β, TNF-α, and IL-6) '
''it means all these sequences are happening when GSK-3beta is unhpshorylatd/activated, so we need to phosphorylate/deactivate GSK-3beta in order to avchive anti-inflamatory effects which is prequisite in metabolic syndrome. Additionally GSK-3beta has shown to mitigate insulin resistance, which again confirm that inactivation/phophorylation of GSK-3beta is prerquisite for acting against metabolic syndrome.
GSK-3beta act by phosphorylation/deactivation of GSK-3beta at ser9 domain.
in brief, Akt/PI3K/PKA/Wnt and as mentioned by John Patrick Alao, mTOR pathways should be considered
You may refer to : Song WJ, Song EA, Jung MS, Choi SH, Baik HH, Jin BK, Kim JH, Chung SH. Phosphorylation and Inactivation of GSK3β by Dual-Specificity Tyrosine (Y)-Phosphorylation-Regulated Kinase 1A (Dyrk1A). Journal of Biological Chemistry. 2014 Dec 4:jbc-M114.
regards,
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