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Role and Regulation of Methionine Sulfoxide Reductase (Msr) in a model of oxidative stress tolerance: Trachemys scripta

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Date Issued:
2018
Abstract/Description:
The detrimental effects of oxidative stress caused by the accumulation of Reactive Oxygen Species (ROS) have been acknowledged as major factors in aging, senescence and several neurodegenerative diseases and conditions such as Parkinson’s disease and stroke (ischemia/reperfusion). Mammalian models are extremely susceptible to these stresses that follow the restoration of oxygen after anoxia; however, some organisms including the freshwater turtle Trachemys scripta can withstand several bouts of anoxia and repeated reoxygenation without any apparent pathology. T. scripta thus provides us with an alternate vertebrate model in which we can investigate physiological mechanisms of neuroprotection without the damaging effects that come with oxidative stress. The major objective of this study was to investigate the protective mechanisms in the turtle brain under conditions of anoxia and oxidative stress. Specifically, the focus is on the Methionine Sulfoxide Reductase system (Msr), an antioxidant and cellular repair system, and how it is regulated to protect the brain against such stressors. Previous studies in my lab have demonstrated that Msr mRNA and protein levels are differentially upregulated during anoxia and reoxygenation. To investigate the regulation of Msr, FOXO3a was directly induced by transfecting a human FOXO3a plasmid into turtle brain cell cultures, as FOXO3a has been shown to regulate MsrA levels in other animal models. Pharmacological manipulation of FOXO3a was also performed using the green tea extract Epigallocatechin gallate (EGCG) as it has been shown to increase expression of FOXO3a during oxidative stress conditions in other models. I found that an induction of human FOXO3a increased FOXO3a levels and showed protection against cell death during oxidative stress. Furthermore, treatment of cells with EGCG increased expression of FOXO3a only when the cells were exposed to oxidative stress and decreased cell death. Induction of FOXO3a and EGCG treatment did not increase MsrA levels, however MsrB3 levels were upregulated under both treatments but only in the presence of oxidative stress. These results suggest that MsrA and MsrB3 protect the cells from oxidative stress damage through different molecular pathways and that EGCG may be a therapeutic target to treat diseases related to damage by oxidative stress.
Title: Role and Regulation of Methionine Sulfoxide Reductase (Msr) in a model of oxidative stress tolerance: Trachemys scripta.
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Name(s): Reiterer, Melissa, author
Milton, Sarah, Thesis advisor
Florida Atlantic University, Degree grantor
Charles E. Schmidt College of Science
Department of Biological Sciences
Type of Resource: text
Genre: Electronic Thesis Or Dissertation
Date Created: 2018
Date Issued: 2018
Publisher: Florida Atlantic University
Place of Publication: Boca Raton, Fla.
Physical Form: application/pdf
Extent: 114 p.
Language(s): English
Abstract/Description: The detrimental effects of oxidative stress caused by the accumulation of Reactive Oxygen Species (ROS) have been acknowledged as major factors in aging, senescence and several neurodegenerative diseases and conditions such as Parkinson’s disease and stroke (ischemia/reperfusion). Mammalian models are extremely susceptible to these stresses that follow the restoration of oxygen after anoxia; however, some organisms including the freshwater turtle Trachemys scripta can withstand several bouts of anoxia and repeated reoxygenation without any apparent pathology. T. scripta thus provides us with an alternate vertebrate model in which we can investigate physiological mechanisms of neuroprotection without the damaging effects that come with oxidative stress. The major objective of this study was to investigate the protective mechanisms in the turtle brain under conditions of anoxia and oxidative stress. Specifically, the focus is on the Methionine Sulfoxide Reductase system (Msr), an antioxidant and cellular repair system, and how it is regulated to protect the brain against such stressors. Previous studies in my lab have demonstrated that Msr mRNA and protein levels are differentially upregulated during anoxia and reoxygenation. To investigate the regulation of Msr, FOXO3a was directly induced by transfecting a human FOXO3a plasmid into turtle brain cell cultures, as FOXO3a has been shown to regulate MsrA levels in other animal models. Pharmacological manipulation of FOXO3a was also performed using the green tea extract Epigallocatechin gallate (EGCG) as it has been shown to increase expression of FOXO3a during oxidative stress conditions in other models. I found that an induction of human FOXO3a increased FOXO3a levels and showed protection against cell death during oxidative stress. Furthermore, treatment of cells with EGCG increased expression of FOXO3a only when the cells were exposed to oxidative stress and decreased cell death. Induction of FOXO3a and EGCG treatment did not increase MsrA levels, however MsrB3 levels were upregulated under both treatments but only in the presence of oxidative stress. These results suggest that MsrA and MsrB3 protect the cells from oxidative stress damage through different molecular pathways and that EGCG may be a therapeutic target to treat diseases related to damage by oxidative stress.
Identifier: FA00013154 (IID)
Degree granted: Dissertation (Ph.D.)--Florida Atlantic University, 2018.
Collection: FAU Electronic Theses and Dissertations Collection
Note(s): Includes bibliography.
Subject(s): Methionine Sulfoxide Reductases
Oxidative Stress
Trachemys scripta
Held by: Florida Atlantic University Libraries
Sublocation: Digital Library
Persistent Link to This Record: http://purl.flvc.org/fau/fd/FA00013154
Use and Reproduction: Copyright © is held by the author with permission granted to Florida Atlantic University to digitize, archive and distribute this item for non-profit research and educational purposes. Any reuse of this item in excess of fair use or other copyright exemptions requires permission of the copyright holder.
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Host Institution: FAU
Is Part of Series: Florida Atlantic University Digital Library Collections.