The Role of Glycogen Synthase Kinase-3β in the Regulation of Mitochondrial Membrane Permeability

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dc.contributor.advisorPatrick R. Cammarata
dc.creatorBrooks, Morgan M.
dc.date.accessioned2019-08-22T19:57:42Z
dc.date.available2019-08-22T19:57:42Z
dc.date.issued2014-12-01
dc.date.submitted2015-06-17T10:30:06-07:00
dc.description.abstractLens epithelial cells in a fully mature lens thrive in a hypoxic environment by developing several pro-survival mechanisms that can prevent cellular dysfunction. Many of these mechanisms focus on maintaining mitochondrial membrane integrity. Loss of integrity of either the inner or outer mitochondrial membrane results in the dissipation of the mitochondrial electrochemical gradient in a process termed mitochondrial membrane permeability transition (mMPT). The project herein focuses primarily on understanding the role of glycogen synthase kinase-3β (GSK-3β) in preventing mMPT in human lens epithelial (HLE-B3) cells; and, understanding that role in relation to extracellular signal-regulated kinase 1/2 (ERK1/2), a known regulator of GSK-3β activity. These studies further define mitoprotective mechanisms of lens cells by identifying how ERK1/2 and GSK-3β can directly (through the mitochondrial transition pore) or indirectly (through the induction of apoptosis) effect mitochondrial membrane potential). Additionally, we extended the GSK-3β studies into the field of epithelial to mesenchymal transition (EMT) research. Specifically we focused on understanding how GSK-3β in conjunction with the hypoxia inducible factor (HIF) proteins can influence the persistence of EMT and the production of vascular endothelial growth factor (VEGF). Collectively, these studies demonstrate important roles in lens epithelial cell mitoprotection for GSK-3β and ERK1/2; and, demonstrate a pivotal role for HIF-1α in the persistence of EMT under hypoxic conditions. Overall, the work described herein has provided invaluable information and understanding in the field of mitoprotection research as well as EMT research.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/27413
dc.language.isoen
dc.provenance.legacyDownloads43
dc.subjectBiochemical Phenomena, Metabolism, and Nutrition
dc.subjectChemical Actions and Uses
dc.subjectGenetics
dc.subjectMacromolecular Substances
dc.subjectMedical Sciences
dc.subjectMedicine and Health Sciences
dc.subjectPharmacology
dc.subjectlenticular mitoprotection
dc.subjectGSK-3 Beta
dc.subjectmitochondria
dc.subjectcell survival
dc.subjectmitochondrial depolarization
dc.subjectlens epithelium
dc.titleThe Role of Glycogen Synthase Kinase-3β in the Regulation of Mitochondrial Membrane Permeability
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineCell Biology and Genetics
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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