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Title: The role of NF-kB in the response to reoxygenation-induced oxidative stress
Authors: Park, Catherine Vida
Issue Date: 2018
Publisher: Newcastle University
Abstract: Hypoxia followed by rapid reoxygenation within the body can lead to cell and tissue damage through the production of reactive oxygen species (ROS) and the resulting oxidative stress. This ischemia and reperfusion is associated with a number of common human diseases such as cancer, stroke and cardiovascular conditions. The cellular response to oxidative stress is characterised by post-translational modification and changes in gene expression. This project focusses on how oxidative stress induced by hypoxia and rapid reoxygenation affects the activation of NF-κB; a rapidly-acting transcription factor that plays a key role in the eukaryotic cell response to infection, radiation and oxidative stress. NF-κB is perpetually activated in a variety of common human diseases such as heart disease, chronic inflammation and cancer; conditions that are also associated with oxidative stress. Investigations presented in this thesis demonstrate the profound effects that hypoxia and reoxygenation have on cell biology, as well as highlighting how these opposite stimuli are so closely connected. The effects of hypoxia and reoxygenation on the cell cycle, DNA damage, cell proliferation and cell survival are all explored in this project, giving great insight into the possible mechanisms at work in response to these stresses. It has been demonstrated previously that certain members of the phosphatidylinositol 3-kinase-related kinase (PIKK) family such as Ataxia Telangiectasia-Mutated (ATM) are able to coordinate the activation of NF-κB pathways in response to specific stimuli such as following DNA damage or oxidative stress. This project has identified a novel role of another member of this family, Ataxia Telangiectasia and Rad-3-related protein (ATR) in the NF-κB response to reoxygenation-induced oxidative stress.
Description: PhD Thesis
Appears in Collections:Institute for Cell and Molecular Biosciences

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