"As shown in Figure XREF_FIG, the inhibition of the mTOR signal by RAPA decreased hypoxia inducible factor 1-alpha (HIF-alpha) and glucose uptake and therefore decreased glycolysis."
"In summary, inactivation of the mTOR and P70S6K pathway by REDD1 and hypoxia leads to increased PP2A function, PHD2 dephosphorylation, and, thus, HIF1alpha stabilization."
"This LKB1 dependent reprogramming of cell metabolism is dependent on the hypoxia inducible factor-1alpha (HIF-1alpha), which accumulates under normoxia in LKB1 deficient cells and is antagonized by inhibition of mTOR complex I signaling."
"Furthermore, the inhibitors of PI3K and mTOR, PI3K and AKT, and ERK 1/2 pathways did not attenuate increased HIF-1alpha protein by bilirubin treatment in HK2 cells."
"Finally, the inhibition of the mTOR pathway prevented the HIF-1alpha activation induced by CM."
"Based on these data and other results not discussed here, we propose a model whereby tPA either released in the synaptic cleft following the onset of cerebral ischemia or intravenously administered interacts with LRP1, leading to NMDAR mediated mTOR activation, mTOR induced HIF-1alpha accumulation, HIF-1alpha-induced recruitment of the neuronal transporter of glucose GLUT3 to the neuronal plasma membrane, and GLUT3 mediated uptake of glucose by neurons in the ischemic brain."
"Drugs may also act indirectly by antibody binding of elevated levels of extracellular angiogenic growth factors eg, bevacizumab (Avastin (R), Genentech), acting on overexpressed receptors on tumor cells themselves eg, sunitinib, sorafenib (Nexavar (R), Bayer) or by inhibiting related pathways such as mTOR upregulation of VEGF and HIF1alpha eg, temsirolimus (Torisel (R), Wyeth)."
"In some cell types, mTOR may also promote HIF-1alpha stabilization and/or TAD function, although the molecular mechanisms are not completely understood."
"We demonstrated that MB induced neuronal protection is mediated via activation of HIF-1, and proposed that MB stabilizes and increases HIF-1, a regulatory subunit of HIF-1 by 1) increasing glucose metabolism, culminating in increased endogenous pyruvate, which is consistent with increased ATP concentration, 2) activating EPO and mTOR signaling pathways, and 3) stimulating nuclear localization of HIF-1alpha."
"We further explored whether PI3K, Akt, and mTOR signals were involved in adiponectin induced HIF-1alpha activation in human chondrosarcoma cells."