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Title: The role of methionine sulfoxide reductase in thermal stress response.
Creator: Martin, James, Bruce, Lindsay, Schey, Karin, Binninger, David
Date Issued: 2013-04-05
PURL: http://purl.flvc.org/fcla/dt/3361149
Subject Headings: Hyperthermia, Heat shock proteins, Methionine, Oxidative stress
Format: Document (PDF)

Title: Alternative Biological Roles of Methionine Sulfoxide Reductases in Drosophila melanogaster.
Creator: Wilson, Kelsey, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The oxidation of methionine (Met) into methionine sulfoxide (met-(o)) leads to deleterious modifications to a variety of cellular constituents. These deleterious alterations can be reversed by enzymes known as methionine sulfoxide reductases (Msr). The Msr (MsrA and MsrB) family of enzymes have been studied extensively for their biological roles in reducing oxidized Met residues back into functional Met. A wide range of studies have focused on Msr both in vivo and in vitro using a variety of...
Show moreThe oxidation of methionine (Met) into methionine sulfoxide (met-(o)) leads to deleterious modifications to a variety of cellular constituents. These deleterious alterations can be reversed by enzymes known as methionine sulfoxide reductases (Msr). The Msr (MsrA and MsrB) family of enzymes have been studied extensively for their biological roles in reducing oxidized Met residues back into functional Met. A wide range of studies have focused on Msr both in vivo and in vitro using a variety of model organisms. More specifically, studies have noted numerous processes affected by the overexpression, under expression, and silencing of MsrA and MsrB. Collectively, the results of these studies have shown that Msr is involved in lifespan and the management of oxidative stress. More recent evidence is emerging that supports existing biological functions of Msr and theorizes the involvement of Msr in numerous biological pathways.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00005980
Subject Headings: Drosophila melanogaster, Methionine Sulfoxide Reductases, Oxidative stress
Format: Document (PDF)

Title: A Study on the Potential Role of Stress Granules and Processing Bodies in Eliminating Oxidatively Damaged RNA.
Creator: Pourkalbassi, Delaram, Li, Zhongwei, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: Oxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and...
Show moreOxidative stress (OS) is strongly implicated in age-related neurodegeneration and other diseases. Under OS, the production of excessive oxidants leads to increased damages to cellular components. Recently, RNA has been discovered as a major target of oxidative damage, including the creation of abasic sites. In this work, we developed a method for quantifying abasic RNA in cell. Using this method, we have examined the potential role of the RNA-processing cellular foci, stress granule (SG) and processing bodies (PB) in eliminating abasic RNA in situ. We demonstrated that RNA is a major target of oxidative damage, constituting the majority of OS-induced abasic nucleic acids in HeLa cell. Importantly, the level of abasic RNA is strongly correlated with SG abundance. Furthermore, inhibition of SG/PB formation causes accumulation of abasic RNA, suggesting that SG/PB participates in removing oxidized RNA and protects cells under OS, which offers novel targets for therapeutic intervention in age-related diseases.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004702
Subject Headings: Aging -- Physiological aspects., Oxidative stress., RNA -- Metabolism.
Format: Document (PDF)

Title: Unraveling the molecular mechanism of human polynucleotide phosphorylase (hPNPase) in controlling oxidized RNA.
Creator: Malla, Sulochan, Li, Zhongwei, Florida Atlantic University, Department of Biomedical Science, Charles E. Schmidt College of Science
Abstract/Description: Oxidation by reactive oxygen species is the major source of RNA damaging insult in living organisms. Increased RNA oxidation has been strongly implicated in a wide range of human diseases; predominantly neurodegeneration. Oxidized RNA should be removed from the cellular system to prevent their deleterious effect to the cells and organisms. In eukaryotic cells, mitochondria are the major intracellular sources of ROS and may cause greater damage to the mitochondrial RNA. In this study, we first...
Show moreOxidation by reactive oxygen species is the major source of RNA damaging insult in living organisms. Increased RNA oxidation has been strongly implicated in a wide range of human diseases; predominantly neurodegeneration. Oxidized RNA should be removed from the cellular system to prevent their deleterious effect to the cells and organisms. In eukaryotic cells, mitochondria are the major intracellular sources of ROS and may cause greater damage to the mitochondrial RNA. In this study, we first investigated the RNA oxidation, by measuring the level of 8-hydroxy-Guanosine (8-oxo-Guo), inside mitochondria and cytoplasm in cultured human cells. We discovered that the mitochondrial 8-oxo-Guo is higher than its cytoplasmic counterparts under both normal growth and oxidative stress condition. Next, we explored the role of human polynucleotide phosphorylase (hPNPase) in controlling RNA oxidation inside mitochondria and cytoplasm. hPNPase binds to oxidized RNA with higher affinity, reduces the 8-oxo-Guo level in total RNA and protects cells against oxidative stress. In this study, the molecular mechanism of hPNPase in 8-oxo-Guo reduction was investigated. First, the effect of hPNPase activities on the 8-oxo-Guo level in mitochondria and cytoplasm was examined. The knockdown of hPNPase increased both the mitochondrial and cytoplasmic 8-oxo-Guo, whereas overexpression had the opposite effect. Second, our study revealed that hSUV3, an RNA helicase that forms a functional complex with hPNPase in mitochondria, was dispensable in reducing 8-oxo-Guo levels.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013392
Subject Headings: RNA, Reactive Oxygen Species, Mitochondria, Oxidative stress
Format: Document (PDF)

Title: Role and Regulation of Methionine Sulfoxide Reductase (Msr) in a model of oxidative stress tolerance: Trachemys scripta.
Creator: Reiterer, Melissa, Milton, Sarah, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
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...
Show moreThe 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.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013154
Subject Headings: Methionine Sulfoxide Reductases, Oxidative Stress, Trachemys scripta
Format: Document (PDF)

Title: Neuroprotection During Acute Oxidative Stress: Role of the PKG Pathway and Identification of Novel Neuromodulatory Agents Using Drosophila Melanogaster.
Creator: Caplan, Stacee Lee, Dawson-Scully, Ken, Milton, Sarah L., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Oxidant stress and injury is inherent in many human diseases such as ischemic vascular and respiratory diseases, heart failure, myocardial infarction, stroke, perinatal and placental insufficiencies, diabetes, cancer, and numerous psychiatric and neurodegenerative disorders. Finding novel therapeutics to combat the deleterious effects of oxidative stress is critical to create better therapeutic strategies for many conditions that have few treatment options. This study used the anoxia-tolerant...
Show moreOxidant stress and injury is inherent in many human diseases such as ischemic vascular and respiratory diseases, heart failure, myocardial infarction, stroke, perinatal and placental insufficiencies, diabetes, cancer, and numerous psychiatric and neurodegenerative disorders. Finding novel therapeutics to combat the deleterious effects of oxidative stress is critical to create better therapeutic strategies for many conditions that have few treatment options. This study used the anoxia-tolerant fruit fly, Drosophila melanogaster, to investigate endogenous cellular protection mechanisms and potential interactions to determine their ability to regulate synaptic functional tolerance and cell survival during acute oxidative stress. The Drosophila larval neuromuscular junction (NMJ) was used to analyze synaptic transmission and specific motor axon contributions. Drosophila Schneider 2 (S2) cells were used to assess viability. Acute oxidative stress was induced using p harmacological paradigms that generate physiologically relevant oxidant species: mitochondrial superoxide production induced by sodium azide (NaN3) and hydroxyl radical formation via hydrogen peroxide (H2O2). A combination of genetic and pharmacological approaches were used to explore the hypothesis that endogenous protection mechanisms control cellular responses to stress by manipulating ion channel conductance and neurotransmission. Furthermore, this study analyzed a group of marine natural products, pseudopterosins, to identify compounds capable of modulating synaptic transmission during acute oxidative stress and potential novel neuromodulatory agents.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004487, http://purl.flvc.org/fau/fd/FA00004487
Subject Headings: Drosophila melanogaster -- Life cycles, Oxidative stress -- Ecophysiology, Oxidative stress -- Prevention, Protein kinases, Proteins -- Chemical modification
Format: Document (PDF)

Title: The NSAID, Sulindac confers protection against oxidative stress induced damage in retinal pigmented epithelial cells.
Creator: Sur, Arunodoy, Biswal, Manas, Kreymerman, Alexander, Weissbach, Herbert, Prentice, Howard, Blanks, Janet C., Graduate College
Date Issued: 2011-04-08
PURL: http://purl.flvc.org/fcla/dt/3164798
Subject Headings: Nonsteroidal anti-inflammatory agents, Oxidative stress, Epithelial cells
Format: Document (PDF)

Title: Sulindac enhances the killing of cancer cells exposed to oxidative stress.
Creator: Kreymerman, Alexander, Ayyanathan, Kasirajan, Kesaraju, Shailaja, Dawson-Scully, Ken, Weissbach, Herbert, Graduate College
Date Issued: 2011-04-08
PURL: http://purl.flvc.org/fcla/dt/3164545
Subject Headings: Nonsteroidal anti-inflammatory agents, Oxidative stress, Mitochondrial pathology
Format: Document (PDF)

Title: Approaches for raising the level of FOXO3a in animal cells.
Creator: Navarro, Diana., Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: The turtle is a unique model of anoxic survival. The turtle's brain can tolerate total oxygen deprivation for hours to days as well as prevent high levels of mitochondrial-derived free radicals upon re-oxygenation. Because of its ability to prevent elevated free radical generation, the turtle has also become recognized as a model of exceptional longevity. We are employing the turtle model for an investigation into the regulation of a key antioxidant enzyme system - methionine sulfoxide...
Show moreThe turtle is a unique model of anoxic survival. The turtle's brain can tolerate total oxygen deprivation for hours to days as well as prevent high levels of mitochondrial-derived free radicals upon re-oxygenation. Because of its ability to prevent elevated free radical generation, the turtle has also become recognized as a model of exceptional longevity. We are employing the turtle model for an investigation into the regulation of a key antioxidant enzyme system - methionine sulfoxide reductases (Msrs), primarily MsrA and MsrB. The Msr system is capable of reversing oxidation of methionines in proteins and Msr subtypes have been implicated in protecting tissues against oxidative stress, as well as, enhancing the longevity of organisms from yeast to mammals. Preliminary data, unpublished results, indicate that MsrA protein and transcripts are elevated by anoxia. A recent study on Caenorhabditis elegans demonstrated that FOXO is involved in activation of the MsrA promoter. Using the turtle MsrA promoter sequence we worked to determine which regions in the promoter are necessary for activation by anoxia. The results of the present study were 1) to prepare a TAT-FOXO3a fusion protein which could penetrate animal cells and 2) to construct a FOXO3a expression vector for transcription studies on MsrA expression.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3342243
Subject Headings: Cellular signal transduction, Cell proliferation, Oxidative stress, Prevention, Adaptation (Physiology)
Format: Document (PDF)

Title: cGMP/PKG-regulated mechanisms of protection from low oxygen and oxidative stress.
Creator: Mahneva, Olena, Milton, Sarah L., Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Stroke is one of the leading causes of human death in the United States. The debilitating effects of an ischemic stroke are due to the fact that mammalian neurons are highly susceptible to hypoxia and subsequent oxygen reperfusion. From studies in Drosophila melanogaster, cGMP-dependent Protein Kinase (PKG) enzyme is thought to affect anoxia tolerance by modifying the electrical current through potassium ion channels. In this research, two animal models were employed: Drosophila melanogaster...
Show moreStroke is one of the leading causes of human death in the United States. The debilitating effects of an ischemic stroke are due to the fact that mammalian neurons are highly susceptible to hypoxia and subsequent oxygen reperfusion. From studies in Drosophila melanogaster, cGMP-dependent Protein Kinase (PKG) enzyme is thought to affect anoxia tolerance by modifying the electrical current through potassium ion channels. In this research, two animal models were employed: Drosophila melanogaster and mammalian neurons exposed to stroke-like conditions. First, in vivo studies using Drosophila were performed to further our knowledge about the differences between the naturally occurring variants of the Drosophila foraging gene, which shows different protein levels of PKG. Mitochondrial density and metabolic activity between two fly genotypes exposed to anoxia and reoxygenation were compared. It was found that flies with less enzyme potentially showed mitochondrial biogenesis and higher metabolic rates upon reoxygenation. Next, in vivo studies where PKG enzyme was activated pharmacologically were performed; it was found that the activation of the cGMP/PKG pathway led to neuroprotection upon anoxia and reoxygenation. Furthermore, this model was translated into the in vitro model using Drosophila cells. Instead of anoxia and reoxygenation, hypoxia mimetics and hydrogen peroxide were used to induce cellular injury. After showing the cGMP/PKG pathway activation-induced cell protection, the potential downstream targets of the molecular signaling as well as underlying biochemical changes were assessed. It was found that mitochondrial potassium ion channels were involved in the protective signaling and the signaling modulated metabolic function. Furthermore, it was found that acidosis protected Drosophila cells from cell death, metabolic disruption, and oxidative stress. Finally, this research was translated to a mammalian in vitro model of neuronal damage upon stroke-like conditions; there, it was demonstrated that the cGMP/PKG pathway activation in rat primary cortical neurons and human cortical neurons was protective from low oxygen and acute oxidative stress. The results of this study lead to a better understanding of molecular mechanisms taking place during low oxygen and oxidative stresses. Consequently, this knowledge may be used to identify potential therapeutic targets and treatments that may prevent detrimental neurological effects of an ischemic stroke in humans.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013013
Subject Headings: Stroke, Cyclic GMP-Dependent Protein Kinases, Oxidative Stress
Format: Document (PDF)

Title: The Effects of MsrA and MsrB in Anoxia Tolerance in Aging Drosophila melanogaster.
Creator: Suthakaran, Nirthieca, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Sciences
Abstract/Description: Drosophila melanogaster tolerates several hours of anoxia (the absence of oxygen) by entering a protective coma. A burst of reactive oxygen species (ROS) is produced when oxygen is reintroduced to the cells. ROS causes oxidative damage to critical cellular molecules, which contribute to aging and development of certain agerelated conditions. The amino acid, methionine, is susceptible to oxidation, although this damage can be reversed by methionine sulfoxide reductases (Msr). This project...
Show moreDrosophila melanogaster tolerates several hours of anoxia (the absence of oxygen) by entering a protective coma. A burst of reactive oxygen species (ROS) is produced when oxygen is reintroduced to the cells. ROS causes oxidative damage to critical cellular molecules, which contribute to aging and development of certain agerelated conditions. The amino acid, methionine, is susceptible to oxidation, although this damage can be reversed by methionine sulfoxide reductases (Msr). This project investigates the effect of Msr-deficiency on anoxia tolerance in Drosophila throughout the lifespan of the animal. The data show that the time for recovery from the protective comma as well as the survival of the animals lacking any Msr activity depends on how quickly the coma is induced by the anoxic conditions. Insight into the roles(s) of Msr genes under anoxic stress can lead us to a path of designing therapeutic drugs around these genes in relation to stroke.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013046
Subject Headings: Drosophila melanogaster, Methionine Sulfoxide Reductases, Anoxia, Aging, Oxidative stress
Format: Document (PDF)

Title: Taurine protection of PC12 cells against endoplasmic reticulum stress induced by oxidative stress.
Creator: Pan, Chunliu, Giraldo, Grace S., Prentice, Howard, Wu, Jang-Yen
Date Issued: 2010-08-24
PURL: http://purl.flvc.org/fcla/dt/3327276
Subject Headings: Oxidative Stress, Oxidative Stress --drug effects, Oxidative Stress --physiology, Antioxidants --pharmacology, Apoptosis Regulatory Proteins, Proto-Oncogene Proteins c-bcl-2, PC12 Cells --drug effects, Endoplasmic Reticulum --drug effects, Transcription Factor CHOP, Taurine
Format: Document (PDF)

Title: Caloric restriction in Drosophila melanogaster.
Creator: Hoxha, Sany., Harriet L. Wilkes Honors College
Abstract/Description: Caloric restriction (CR), the reduction of nutrient intake short of malnutrition, extends the lifespan of various organisms and can improve measures of human health. Whether mechanisms of lifespan extension are conserved between humans and model organisms is unknown. In mammals, implementing CR is easily achieved by providing a restricted group with a fraction of the food consumed by an "ad libitum" fed group, which has unlimited food access. Due to the difficulty in directly controlling...
Show moreCaloric restriction (CR), the reduction of nutrient intake short of malnutrition, extends the lifespan of various organisms and can improve measures of human health. Whether mechanisms of lifespan extension are conserved between humans and model organisms is unknown. In mammals, implementing CR is easily achieved by providing a restricted group with a fraction of the food consumed by an "ad libitum" fed group, which has unlimited food access. Due to the difficulty in directly controlling Drosophila food intake, caloric restriction, performed similarly to the mammalian paradigm, has never been tested in flies. Here, we demonstrate a system that allows measurement of food intake throughout life. This system will be used to measure fly lifespan under caloric restriction analogous to current mammalian studies. Our work will help tease apart the differences between the various caloric and dietary restriction paradigms in Drosophila, strengthening our understanding of how fly models relate to mammalian systems.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3359316
Subject Headings: Aging, Physiological aspects, Nutrition disorders in old age, Oxidative stress, Pathophysiology
Format: Document (PDF)

Title: Developmental delays in methionine sulfoxide reductase mutants in Drosophila Melanogaster.
Creator: Hausman, William, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Aging is a biological process that has many detrimental effects due to the accumulation of oxidative damage to key biomolecules due to the action of free radicals. Methionine sulfoxide reductase (Msr) functions to repair oxidative damage to methionine residues. Msr comes in two forms, MsrA and MsrB, each form has been shown to reduce a specific enantiomer of bound and free oxidized methionine. Effects of Msr have yet to be studied in the major developmental stages of Drosophila melanogaster...
Show moreAging is a biological process that has many detrimental effects due to the accumulation of oxidative damage to key biomolecules due to the action of free radicals. Methionine sulfoxide reductase (Msr) functions to repair oxidative damage to methionine residues. Msr comes in two forms, MsrA and MsrB, each form has been shown to reduce a specific enantiomer of bound and free oxidized methionine. Effects of Msr have yet to be studied in the major developmental stages of Drosophila melanogaster despite the enzymes elevated expression during these stages. A developmental timeline was determined for MsrA mutant, MsrB mutant, and double null mutants against a wild type control. Results show that the Msr double mutant is delayed approximately 20 hours in the early/mid third instar stage while each of the single mutants showed no significant difference to the wild type. Data suggests that the reasoning of this phenomenon is due to an issue gaining mass.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004200, http://purl.flvc.org/fau/fd/FA00004200
Subject Headings: Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress
Format: Document (PDF)

Title: aB- crystallin/sHSP is required for mitochondrial function in human ocular tissue.
Creator: McGreal, Rebecca., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The central premise of this dissertation is that the small heat shock protein (sHSP), (Sa(BB-crystallin is essential for lens and retinal pigmented epithelial (RPE) cell function and oxidative stress defense. To date, the mechanism by which it confers protection is not known. We hypothesize that these functions could occur through its ability to protect mitochondrial function in lens and RPE cells. To test this hypothesis, we examined the expression of (Sa(BB-crystallin/sHSP in lens and RPE...
Show moreThe central premise of this dissertation is that the small heat shock protein (sHSP), (Sa(BB-crystallin is essential for lens and retinal pigmented epithelial (RPE) cell function and oxidative stress defense. To date, the mechanism by which it confers protection is not known. We hypothesize that these functions could occur through its ability to protect mitochondrial function in lens and RPE cells. To test this hypothesis, we examined the expression of (Sa(BB-crystallin/sHSP in lens and RPE cells, we observed its localization in the cells, we examined translocation to the mitochondria in these cells upon oxidative stress treatment, we determined its ability to form complexes with and protect cytochrome c (cyt c) against damage, and we observed its ability to preserve mitochondrial function under oxidative stress conditions in lens and RPE cells. In addition to these studies, we examined the effect of mutations of (Sa(BB-crystallin/sHSP on its cellular localization and translocation patterns under oxidative stress, its in vivo and in vitro chaperone activity, and its ability to protect cyt c against oxidation. Our data demonstrated that (Sa(BB-crystallin/sHSP is expressed at high levels in the mitochondria of lens and RPE cells and specifically translocates to the mitochondria under oxidative stress conditions. We demonstrate that (Sa(BB-crystallin/sHSP complexes with cyt c and protects it against oxidative inactivation. Finally, we demonstrate that (Sa(BB-crystallin/sHSP directly protects mitochondria against oxidative inactivation in lens and RPE cells. Since oxidative stress is a key component of lens cataract formation and age-related macular degeneration (AMD), these data provide a new paradigm for understanding the etiology of these diseases.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3342242
Subject Headings: Mitochondrial pathology, Chemical mutagenesis, Oxidative stress, Prevention, Cellular signal transduction, Eye, Diseases, Etiology, Molecular chaperones
Format: Document (PDF)

Title: Protecting Synaptic Function From Acute Oxidative Stress: A Novel Role For Big K+ (BK) Channels And Resveratrol-Like Compounds.
Creator: Bollinger, Wesley L., Dawson-Scully, Ken, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Oxidative stress causes neural damage and inhibits essential cellular processes, such as synaptic transmission. Despite this knowledge, currently available pharmaceutical agents cannot effectively protect neural cells from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries in a real life clinical setting. Our lab has developed an electrophysiology protocol to identify novel drugs that protect an essential cellular process (neurotransmission) from acute...
Show moreOxidative stress causes neural damage and inhibits essential cellular processes, such as synaptic transmission. Despite this knowledge, currently available pharmaceutical agents cannot effectively protect neural cells from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries in a real life clinical setting. Our lab has developed an electrophysiology protocol to identify novel drugs that protect an essential cellular process (neurotransmission) from acute oxidative stress-induced damage. Through this doctoral dissertation, we have identified three new drugs, including a Big K+ (BK) K+ channel blocker (iberiotoxin), resveratrol, and a custom made resveratrol-like compound (fly2) that protect synaptic function from oxidative stress-induced insults. Further developing these drugs as neuroprotective agents may prove transformative in protecting the human brain from acute oxidative stress elicited by strokes, heart attacks, and traumatic brain injuries. Inhibiting the protein kinase G (PKG) pathway protects neurotransmission from acute oxidative stress. This dissertation has expanded upon these findings by determining that the PKG pathway and BK K+ channels function through independent biochemical pathways to protect neurotransmission from acute oxidative stress. Taken together, this dissertation has identified two classes of compounds that protect neurotransmission from acute oxidative stress, including resveratrol-like compounds (resveratrol, fly2) and a BK K+ channel inhibitor (iberiotoxin). Further developing these drugs in clinical trials may finally lead to the development of an effective neuroprotective agent.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013054
Subject Headings: Neural transmission., Oxidative stress., Large-Conductance Calcium-Activated Potassium Channels., Neuroprotective Agents.
Format: Document (PDF)

Title: Phenotypic and behavioral effects of methionine sulfoxide reductase deficiency and oxidative stress in Drosophila melanogaster.
Creator: Mulholland, Kori., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Harman's theory of aging proposes that a buildup of damaging reactive oxygen species (ROS) is one of the primary causes of the deleterious symptoms attributed to aging. Cellular defenses in the form of antioxidants have evolved to combat ROS and reverse damage; one such group is the methionine sulfoxide reductases (Msr), which function to reduce oxidized methionine. MsrA reduces the S enantiomer of methionine sulfoxide, Met-S-(o), while MsrB reduces the R enantiomer, Met-R-(o). The focus of...
Show moreHarman's theory of aging proposes that a buildup of damaging reactive oxygen species (ROS) is one of the primary causes of the deleterious symptoms attributed to aging. Cellular defenses in the form of antioxidants have evolved to combat ROS and reverse damage; one such group is the methionine sulfoxide reductases (Msr), which function to reduce oxidized methionine. MsrA reduces the S enantiomer of methionine sulfoxide, Met-S-(o), while MsrB reduces the R enantiomer, Met-R-(o). The focus of this study was to investigate how the absence of one or both forms of Msr affects locomotion in Drosophila using both traditional genetic mutants and more recently developed RNA interference (RNAi) strains. Results indicate that lack of MsrA does not affect locomotion. However, lack of MsrB drastically reduces rates of locomotion in all age classes. Furthermore, creation of an RNAi line capable of knocking down both MsrA and MsrB in progeny was completed.
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Date Issued: 2013
PURL: http://purl.flvc.org/fcla/dt/3362558
Subject Headings: Drosophila melanogaster, Genetics, Aging, Molecular aspects, Oxidative stress, Mitochondrial pathology, Cellular signal transduction, Oxidation-reduction reaction, Biochemical markers, Mutation (Biology)
Format: Document (PDF)

Title: Reduced Reproductivity and Larval Locomotion in the Absence of Methionine Sulfoxide Reductase in Drosophila.
Creator: Singkornrat, Diana, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that...
Show moreThe inevitable aging process can be partially attributed to the accumulation of oxidative damage that results from the action of free radicals. Methionine sulfoxide reductases (Msr) are a class of enzymes that repair oxidized methionine residues. The two known forms of Msr are MsrA and MsrB which reduce the R- and S- enantiomers of methionine sulfoxide, respectively. Our lab has created the first genetic animal model that is fully deficient for any Msr activity. Previously our lab showed that these animals exhibit a 20 hour delay in development of the third instar larvae (unpublished data). My studies have further shown that the prolonged third-instar stage is due to a reduced growth rate associated with slower food intake and a markedly slower motility. These Msr-deficient animals also exhibit decreased egg-laying that can be attributed to a lack of female receptivity to mating.
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004777, http://purl.flvc.org/fau/fd/FA00004777
Subject Headings: Proteins--Chemical modification., Oxidative stress., Oxidation-reduction reaction., Drosophila melanogaster--Genetics., Mitochondrial pathology., Cellular signal transduction., Mutation (Biology), Aging--Molecular aspects.
Format: Document (PDF)

Title: The effect of mutated aconitase on yeast longevity.
Creator: Kwan, Melissa “CJ”, Kirchman, Paul
Date Issued: 2012-04-06
PURL: http://purl.flvc.org/fcla/dt/3350911
Subject Headings: Mitochondrial Proteins, Citric Acid Cycle, Aconitate Hydratase, ACO2 protein, human, Saccharomyces cerevisiae, Oxidative Stress, Yeast Longevity
Format: Document (PDF)

Title: Mitochondrial regulation pathways in the lens: pink1/parkin- and bnip3l-mediated mechanisms.
Creator: Aktan, Kerem, Kantorow, Marc, Florida Atlantic University, Charles E. Schmidt College of Medicine, Department of Biomedical Science
Abstract/Description: The mitochondrion is the powerhouse of the cell. Therefore, it is critical to the homeostasis of the cell that populations of mitochondria that are damaged or in excess are degraded. The process of targeted elimination of damaged or excess mitochondria by autophagy is called mitophagy. In this report, analysis of the mitophagy regulators PINK1/PARKIN and BNIP3L and their roles are assessed in the lens. PARKIN, an E3 ubiquitin ligase, has been shown to play a role in directing damaged...
Show moreThe mitochondrion is the powerhouse of the cell. Therefore, it is critical to the homeostasis of the cell that populations of mitochondria that are damaged or in excess are degraded. The process of targeted elimination of damaged or excess mitochondria by autophagy is called mitophagy. In this report, analysis of the mitophagy regulators PINK1/PARKIN and BNIP3L and their roles are assessed in the lens. PARKIN, an E3 ubiquitin ligase, has been shown to play a role in directing damaged mitochondria for degradation. While BNIP3L, an outer mitochondrial membrane protein, increases in expression in response to excess mitochondria and organelle degradation during cellular differentiation. We have shown that PARKIN is both induced and translocates from the cytoplasm to the mitochondria in human epithelial lens cells upon oxidative stress exposure. In addition, our findings also show that overexpression of BNIP3L causes premature clearance of mitochondria and other organelles, while loss of BNIP3L results in lack of clearance. Prior to this work, PARKIN mediated mitophagy had not been shown to act as a protective cellular response to oxidative stress in the lens. This project also resulted in the novel finding that BNIP3L-mediated mitophagy mechanisms are required for targeted organelle degradation in the lens.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004427, http://purl.flvc.org/fau/fd/FA00004427
Subject Headings: Cellular signal transduction, Eye -- Diseases -- Etiology, Mitochondrial pathology, Mitophagy, Molecular chaperones, Oxidative stress -- Prevention, Protein folding
Format: Document (PDF)

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