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Full-Text Articles in Life Sciences
Regulation Of Igfbp-1 Phosphorylation In Hypoxia Via Mtor Signaling, Ian Damerill
Regulation Of Igfbp-1 Phosphorylation In Hypoxia Via Mtor Signaling, Ian Damerill
Electronic Thesis and Dissertation Repository
In this study, we provide novel evidence for a role of fetal liver mTOR signaling in regulating IGF-I bioavailability by modulating IGFBP-1 phosphorylation due to hypoxia – a key factor in the development of reduced fetal growth in utero. We utilized HepG2 cells in vitro and demonstrated a link between mTOR inhibition and hypoxia-induced IGFBP-1 phosphorylation. Using a biological assay for IGF-I receptor autophosphorylation, we demonstrated a functional significance for hypoxia-induced IGFBP-1 phosphorylation in reducing IGF-I bioactivity in vitro. Further, we have implicated a mechanistic link to increased CK2 activity within this regulation. We demonstrate that mTOR inhibition …
Niacin And Microvascular Endothelial Cell Response To Fatty Acid Excess And Hypoxia, Dominic Pang
Niacin And Microvascular Endothelial Cell Response To Fatty Acid Excess And Hypoxia, Dominic Pang
Electronic Thesis and Dissertation Repository
Niacin can reduce vascular disease risk, but its mechanism of action is controversial, and may not be dependent on systemic lipid modifying effects. This thesis tested the hypothesis that niacin directly improves endothelial cell function under lipotoxic and low oxygen conditions, as seen in ischemic conditions during metabolic syndrome, and investigated the potential mechanism involved. Human microvascular endothelial cell (HMVEC) survival was reduced by exposure to excess fatty acids under both normoxic and low oxygen conditions. Angiogenic function, as determined by tube formation on Matrigel, was impaired during fatty acid overload under either normoxic or low oxygen conditions. These effects …
Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, Priya Patel
Investigating Microenvironmental Regulation Of Human Chordoma Cell Behaviour, Priya Patel
Electronic Thesis and Dissertation Repository
The tumor microenvironment is complex and often includes matricellular proteins and regions of hypoxia, which can promote stem and progenitor properties that regulate cancer cell biology. We hypothesized that hypoxia and CCN2 would promote notochord progenitor-like characteristics in human chordoma (U-CH1) cells, and assessed cell phenotype using Real-time qPCR and in vitro functional assays. We found the expression of CCN family members CCN1, CCN2, CCN3 and CCN5 in U-CH1 cells. We demonstrate that hypoxia and CCN2 promoted progenitor-like characteristics specific to the notochordal tissue of origin. Specifically, hypoxia had the greatest ability to promote progenitor characteristics (increase in notochord markers …