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MANGANESE SUPEROXIDE DISMUTASE INFLUENCE IN
NEURAL INJURY AND SURVIVAL
by
Scott Ornelas Walker
______________________________________________
A Thesis Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
MASTER OF SCIENCE
(PATHOBIOLOGY)
December 2007
Copyright 2007 Scott Ornelas Walker
Object Description
| Title | Manganese superoxide dismutase influence in neural injury and survival |
| Author | Walker, Scott Ornelas |
| Author email | scottwal@usc.edu |
| Degree | Master of Science |
| Document type | Thesis |
| Degree program | Pathobiology |
| School | Keck School of Medicine |
| Date defended/completed | 2007-10-10 |
| Date submitted | 2007 |
| Restricted until | Unrestricted |
| Date published | 2007-12-18 |
| Advisor (committee chair) |
Sadun, Alfredo A. Hofman, Florence M. |
| Advisor (committee member) |
Hinton, David R. Ying, Shao-Yao |
| Abstract | Mitochondrial derangements are a basis for a number of hereditary CNS disorders. Among mitochondial neurodegenerative diseases are those that affect the eye. In one such instance, a mitochondrial derangement manifests with the loss of vision in one eye and then in the other within the time span of a few weeks during the second to third decade of life. Affecting males more than females, this peculiar manifestation has been characterized as what is now known as Leber's Hereditary Optic Neuropathy (LHON). Of the possible explanations for why blindness occurs in this neuropathy, focus was on the effects of pathologic levels of reactive oxygen species (ROS) within the optic nerve (ON). These ROS are thought to overwhelm the native ON antioxidant defenses and lead to axonal cell death within the mammalian optic nerve. In LHON, this condition results in irreversible blindness from optic atrophy. Studies performed on post-mortem human LHON optic nerve tissue revealed axonal drop-out of the smallest diameter axons that gave the initial basis for performing further animal and cell studies into the possible mechanism for optic nerve compromise.; A key player in the mechanism thought to manage the mitochondrial ROS load is the manganese form of superoxide dismutase (MnSOD or SOD2). Superoxide dismutases as an enzyme class protect the cell against oxidative damage and mediate cellular superoxide anion loads. This metalloenzyme is believed to be responsible in large part for the survival against apoptotic pressures in both progenitor and terminally-differentiated neurons within the CNS. The hypothesis of this thesis study assumes mitochondrial health, and in turn, host cell survival, depends on the MnSOD mechanism.; Using both animal and cell models, induction of cell death within the CNS was implemented using an optic nerve crush and an ischemia-reperfusion (IRP) model that revealed both expressional and translational increases in MnSOD response as compared to normals. In rat brain progenitor cell experiments, it was demonstrated that if MnSOD was suppressed, there occurred a concomitant drop in survival relative to normals. Even when dismutase-like function was examined with an SOD-mimetic in retinoblastoma cells exposed to noxious levels of TNF, survival was enhanced. |
| Keyword | manganese superoxide dismutase; SOD2; optic nerve; retinal ganglion cell; Leber's hereditary optic neuropathy; LHON; MnSOD; Sadun |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m984 |
| Contributing entity | University of Southern California |
| Rights | Walker, Scott Ornelas |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | cisadmin@dots.usc.edu |
| Filename | etd-Walker-20071218 |
| Archival file | uscthesesreloadpub_Volume14/etd-Walker-20071218.pdf |
Description
| Title | Page 1 |
| Contributing entity | University of Southern California |
| Repository email | cisadmin@dots.usc.edu |
| Full text | MANGANESE SUPEROXIDE DISMUTASE INFLUENCE IN NEURAL INJURY AND SURVIVAL by Scott Ornelas Walker ______________________________________________ A Thesis Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree MASTER OF SCIENCE (PATHOBIOLOGY) December 2007 Copyright 2007 Scott Ornelas Walker |
