Identification of Oxidized Proteins in Alzheimer's Disease

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dc.contributor.advisorGracy, Robert R.
dc.contributor.committeeMemberHarris, B.
dc.contributor.committeeMemberLacko, Andras G.
dc.creatorChoi, Joungil
dc.date.accessioned2019-08-22T21:09:28Z
dc.date.available2019-08-22T21:09:28Z
dc.date.issued2002-08-01
dc.date.submitted2013-06-27T15:00:08-07:00
dc.description.abstractJoungil Choi, Identification of Oxidized Proteins in Alzheimer’s Disease. Doctor of Philosophy (Molecular Biology and Immunology). August, 2002. Pages-110. Tables 8. Figures 24. Oxidative modification of specific proteins is central to the pathology of Alzheimer’s disease (AD). The purpose of this study was to identify the oxidation-sensitive proteins in neuronal cells, fibroblasts from AD subjects, and in the blood of AD patients. In all cases, age-matched non-Alzheimer’s samples were used as controls. Proteomic methods were used to isolate and characterize the oxidized proteins. These included two-dimensional gel electrophoresis, immunolocalization of oxidized proteins and identification by MALDI-TOF mass spectroscopic methods. It was hypothesized that knowledge of these critical oxidation-sensitive proteins would shed light on the underlying mechanism of the disease. In addition, it was postulated that these proteins might prove to be biomarkers for early detection and monitoring the progress of the disease. The results show that two different oxidative stressors (H2O2 generated enzymatically, or the amyloid beta peptide, AB25-35) induce apoptotic cell death and oxidation of specific proteins (heat shock protein 60 and vimentin) in skin fibroblasts from AD subjects and in neuronal cells. In addition, the results indicate that susceptibility of these two proteins to oxidative stress is increased in fibroblasts from AD patients, compared to non-AD controls. Pretreatment with antioxidants (e.g., vitamin E or flavonoids) protect these proteins from oxidative damage. Both heat shock protein 60 and vimentin, have been suggested to function as antiapoptotic proteins. Thus, their oxidative damage could lead to the apoptotic neuronal cell death in Alzheimer’s disease. In the blood plasma of AD subjects, isoforms of fibrinogen gamma chain and alpha-1 antitrypsin were found to be oxidized. These proteins exhibited to a two- to six-fold greater specific oxidation index in plasma from AD subjects when compared to controls. Both of these proteins have been suggested to be implicated in oxidation-mediated damage of inflammation in the AD brain.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/20.500.12503/29115
dc.language.isoen
dc.provenance.legacyDownloads1
dc.subjectBiomedical Engineering and Bioengineering
dc.subjectDevelopmental Neuroscience
dc.subjectDiseases
dc.subjectLife Sciences
dc.subjectMedical Neurobiology
dc.subjectMedicine and Health Sciences
dc.subjectMolecular and Cellular Neuroscience
dc.subjectMolecular Biology
dc.subjectNeurology
dc.subjectNeuroscience and Neurobiology
dc.subjectAlzheimer’s Disease
dc.subjectoxidative modification
dc.subjectoxidation-sensitive proteins
dc.subjectneuronal cells
dc.subjectoxidized proteins
dc.subjectH202 generated enzymatically
dc.subjectamyloid beta peptide
dc.subjectAB25-35
dc.subjectapoptotic cell death
dc.titleIdentification of Oxidized Proteins in Alzheimer's Disease
dc.typeDissertation
dc.type.materialtext
thesis.degree.departmentGraduate School of Biomedical Sciences
thesis.degree.disciplineMicrobiology and Immunology
thesis.degree.grantorUniversity of North Texas Health Science Center at Fort Worth
thesis.degree.nameDoctor of Philosophy

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