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dc.contributor.advisorShi, Honglian
dc.contributor.authorGong, Chen
dc.date.accessioned2018-01-28T21:55:19Z
dc.date.available2018-01-28T21:55:19Z
dc.date.issued2016-05-31
dc.date.submitted2016
dc.identifier.otherhttp://dissertations.umi.com/ku:14683
dc.identifier.urihttp://hdl.handle.net/1808/25736
dc.description.abstractIschemic stroke is one of the leading causes of brain injury and death. Many mechanisms underlying ischemia-induced neuronal death have been investigated. Dysregulation of brain iron homeostasis is one of these mechanisms. It is well known that accumulation of intercellular iron in the brain induces free radical production, lipid peroxidation, and DNA damage. The overall aim of this project was to investigate a novel therapeutic mechanism that could be targeted to reduce or prevent iron-induced ischemic brain injury. We hypothesize that heat shock protein 90 (HSP90) plays a role in regulating intracellular iron accumulation upon ischemia and that inhibiting HSP90 rescues the brain from ischemic injury. First, in order to measure iron levels, the function of a newly developed hydroxylamine compound was tested as a ferrous ion probe. We found that this probe was able to indicate the level of ferrous ion both in cells and in solution with high sensitivity and reliability. Few interfering effects were observed by the presence of other metal ions and reducing agents on the iron measurement. KU32 is a HSP90 inhibitor that was used to investigate whether pharmacological inhibition of HSP90 reduced ischemic injury. We found that KU32 decreased levels of intercellular iron and expression of hepcidin, a central iron regulator. In addition, KU32 reduced neuronal death following ischemia. Taken together, this project has found a new method for measuring ferrous iron levels and a possible link among heat shock proteins in cellular iron regulation. These data suggest that targeting HSP90 may be a potential therapeutic approach to reduce ischemia-induced iron neurotoxicity.
dc.format.extent88 pages
dc.language.isoen
dc.publisherUniversity of Kansas
dc.rightsCopyright held by the author.
dc.subjectPharmacology
dc.subject
dc.titleIron regulation and heat shock proteins in ischemic stroke
dc.typeThesis
dc.contributor.cmtememberDobrowsky, Rick T
dc.contributor.cmtememberZhao, Liqin
dc.thesis.degreeDisciplinePharmacology & Toxicology
dc.thesis.degreeLevelM.S.
dc.identifier.orcid
dc.rights.accessrightsopenAccess


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