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Title: Characterization of Methionine Sulfoxide Reductases A and Bs from Tobacco Plant.
Creator: Ding, Di, Zhang, Xing-Hai, Florida Atlantic University
Abstract/Description: One methionine sulfoxide reductase A (TMSRA) and two methionine sulfoxide reductase Bs (TMSRB 1 and TMSRB2) were isolated from tobacco plants. TMSRA showed specificity for the reduction of Met-(S)-SO and both TMSRBs were specific for the reduction of Met-(R)-SO. TMSRA was the cytosolic form and both TMSRBs were plastid forms based on sequence comparison and expression tests. TMSRA and TMSRB2 could use either thioredoxin (TRX) or dithiothreitol (DTT) as reducing system, while TMSRB 1 showed...
Show moreOne methionine sulfoxide reductase A (TMSRA) and two methionine sulfoxide reductase Bs (TMSRB 1 and TMSRB2) were isolated from tobacco plants. TMSRA showed specificity for the reduction of Met-(S)-SO and both TMSRBs were specific for the reduction of Met-(R)-SO. TMSRA was the cytosolic form and both TMSRBs were plastid forms based on sequence comparison and expression tests. TMSRA and TMSRB2 could use either thioredoxin (TRX) or dithiothreitol (DTT) as reducing system, while TMSRB 1 showed little activity with TRX but much more activity with DTT, which was similar to the mitochondrial MSRB2 from mammals. Ferredoxin (FD) is not the reducing system for Msrs, but might reflect the redox status in the cell and control the activity of Msrs indirectly.
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Date Issued: 2006
PURL: http://purl.flvc.org/fau/fd/FA00000746
Subject Headings: Proteins--Chemical modification, Genetic regulation, Plant genetic engineering, Antioxidants
Format: Document (PDF)

Title: Methionine sulfoxide reductase deficiency leads to mitochondrial dysfunction in Drosophila melanogaster.
Creator: Verriotto, Jennifer., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Mitochondria are a major source of reactive oxygen species and are particularly vulnerable to oxidative stress. Mitochondrial dysfunction, methionine oxidation, and oxidative stress are thought to play a role in both the aging process and several neurodegenerative diseases. Two major classes of methionine sulfoxide reductases, designated MsrA and MsrB are enzymes that function to repair the enatiomers of methionine sulfoxide, met-(o)-S and met-(o)- R, respectively. This study focuses on the...
Show moreMitochondria are a major source of reactive oxygen species and are particularly vulnerable to oxidative stress. Mitochondrial dysfunction, methionine oxidation, and oxidative stress are thought to play a role in both the aging process and several neurodegenerative diseases. Two major classes of methionine sulfoxide reductases, designated MsrA and MsrB are enzymes that function to repair the enatiomers of methionine sulfoxide, met-(o)-S and met-(o)- R, respectively. This study focuses on the effect of Msr deficiencies on mitochondrial function by utilizing mutant alleles of MsrA and MsrB. The data show that loss of only one form of Msr in the mitochondria does not completely impair the function of the mitochondria. However, loss of both Msr proteins within the mitochondria leads to an increased ROS production and a diminished energy output of the mitochondria. These results support the hypothesis that Msr plays a key role in proper mitochondrial function.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3174310
Subject Headings: Oxidation-reduction reaction, Proteins, Chemical modification, Genetic regulation
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: Molecular mechanisms of neuroprotection in the anoxia tolerant freshwater turtle.
Creator: Kesaraju, Shailaja., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Cardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of...
Show moreCardiac ischemia, stroke and some neurodegenerative disorders are all characterized by cell damage and death due to low oxygen levels. Comparative studies show that anoxia tolerant model systems present a unique opportunity to study "survival" instead of death in the complete absence of oxygen. The freshwater turtle (Trachemys scripta elegans) is unique in its ability to survive total oxygen deprivation for hours to days, as well as reoxygenation insult after anoxia. The broad objective of this study is to understand the modulation of key molecular mechanisms involving stress proteins and VEGF that offer neuroprotection and enhance cell survival in the freshwater turtle through anoxia and reoxygenation. In vivo analyses have shown that anoxia induced stress proteins (Hsp72, Hsp60, Grp94, Hsp60, Hsp27, HO-1); modest changes in the Bcl2/Bax ratio and no change in cleaved caspase-3 expression suggesting resistance to neuronal damage. These results were corroborated with immunohistochemical evidence indicating no damage in turtle brain when subjected to the stress of anoxia and A/R. To understand the functional role of Hsp72, siRNA against Hsp72 was utilized to knockdown Hsp72 in vitro (neuronally enriched primary cell cultures established from the turtle). Knockdown cultures were characterized by increased cell death associated with elevated ROS levels. Silencing of Hsp72 knocks down the expression of Bcl2 and increases the expression of Bax, thereby decreasing the Bcl2/Bax ratio. However, there was no increase in cytosolic Cytochrome c or the expression levels of cleaved Caspase-3. Significant increase in AIF was observed in the knockdown cultures that increase through anoxia and reoxygenation, suggesting a caspase independent pathway of cell death., Expression of the master regulator of hypoxia, HIF1 alpha and its target gene, VEGF, were analyzed at the mRNA and protein levels. The results showed no significant increase in HIF-1 alpha levels but anoxia VE GF The levels of stress proteins and VEGF returned to control levels during reoxygenation suggesting robust ROS protection mechanisms through reoxygenation. The present study thereby emphasizes Trachemys scripta as an advantageous model to examine anoxia and reoxygenation survival without major damage to the brain due to it's modulation of molecular mechanisms.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/165943
Subject Headings: Turtles, Physiology, Anoxemia, Proteins, Chemical modification, Oxygen, Physiological effect, Molecular neurobiology
Format: Document (PDF)

Title: Methionine sulfoxide reductases: studies on the reducing requirements and role in the metabolism of sulindac.
Creator: Brunell, David J., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is...
Show moreThe methionine sulfoxide reductase (Msr) enzymes catalyze the reduction of methionine sulfoxide (Met(O)) to methionine. The Msr enzymes protect cells against oxidative stress and may have a role in aging. The MsrA family of enzymes reduces stereospecifically the S epimer of free and protein-bound Met(O) while the MsrB family reduces the R epimer of Met(O) in proteins. It has been generally accepted, primarily from studies on MsrA, that the biological reductant for the Msr enzymes is thioredoxin (Trx), although high levels of dithiothreitol (DTT) can be used as the reductant in vitro. In contrast, certain MsrB enzymes show less than 10% of the activity with Trx as compared to DTT. This raises the possibility that in animal cells Trx may not be the direct hydrogen donor for the MsrB enzymes. Studies with bovine liver extracts have shown that thionein, the apoprotein of metallothionein, can function as a reductant for the Msr proteins. Certain selenium compounds such as selenocystamine and selenocystine can also serve as potent reducing agents for the Msr enzymes. Since an increased activity of Msr enzymes can reduce the level of oxidative damage in tissues, compounds that could activate Msr may have therapeutic potential. A high-throughput screening assay has been developed to screen large chemical libraries to find activators of MsrA, as well as specific inhibitors that could be useful research tools. This study will be done in collaboration with The Scripps Florida Research Institute. Sulindac was originally developed as a non-steroidal anti-inflammatory drug but has also shown efficacy in the treatment of certain cancers. The S epimer of sulindac is known to be reduced by MsrA, but the enzymes responsible for reduction of the R epimer are not known., An activity has been purified from rat liver which is capable of reducing the R epimers of sulindac, free Met(O) and a dabsylated Met(O) substrate, the latter suggesting that this enzyme may have properties similar t o the MsrB enzymes. The oxidation of the epimers of sulindac to sulindac sulfone has also been characterized, and the members of the cytochrome P450 family involved in the oxidation have been identified.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/227979
Subject Headings: Cellular signal transduction, Proteins, Chemical modification, Biochemical markers, Oxidation-reduction reaction
Format: Document (PDF)

Title: Peroxiredoxin 3 and Methionine sulfoxide reductase A are Essential for Lens Cell Viability by Preserving Lens Cell Mitochondrial Function through Repair of Cytochrome c.
Creator: Lee, Wanda, Florida Atlantic University, Kantorow, Marc, Charles E. Schmidt College of Science, Department of Biomedical Science
Abstract/Description: The central premise of this dissertation is that mitochondrial antioxidant enzymes are essential to lens cell viability by preserving lens cell mitochondria and protecting and/or repairing lens cell proteins, and two mitochondrial-specific antioxidant enzymes, Peroxiredoxin 3 (PRDX3) and Methionine sulfoxide reductase A (MsrA), are explored. In this dissertation, we will examine the expression ofPRDX3 in the human lens, its colocalization to the lens cell mitochondria, its ability to be...
Show moreThe central premise of this dissertation is that mitochondrial antioxidant enzymes are essential to lens cell viability by preserving lens cell mitochondria and protecting and/or repairing lens cell proteins, and two mitochondrial-specific antioxidant enzymes, Peroxiredoxin 3 (PRDX3) and Methionine sulfoxide reductase A (MsrA), are explored. In this dissertation, we will examine the expression ofPRDX3 in the human lens, its colocalization to the lens cell mitochondria, its ability to be induced by H20 2-oxidative stress, and speculate how PRDX3 function/sf could affect the lens. We will also examine the reduced levels of MsrA by targeted gene silencing and its effect on reactive oxygen species production and mitochondrial membrane potential in human lens cells to determine its role in mitochondrial function in the lens. Lastly, we will examine the ability of MsrA to repair and restore function to a critical mitochondrial protein, Cytochrome c. The collective evidence strongly indicates that the loss of mitochondrial-specific enzymes, such as PRDX3 and MsrA, are responsible for increased reactive oxygen species levels, decreased mitochondrial membrane potential, protein aggregation and lens cell death, and further indicates that mitochondrial repair, protective, and reducing systems play key roles in the progression of age-related cataract and other agerelated diseases.
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Date Issued: 2008
PURL: http://purl.flvc.org/fau/fd/FA00000868
Subject Headings: Genetic regulation, Proteins--Chemical modification, Cellular signal transduction, Eye--Physiology, Mitochondrial pathology
Format: Document (PDF)

Title: Role of Methionine Sulfoxide Reductase (MsrA) on Aging and Oxidative Stress in Drosophila.
Creator: Foss, Katie, Binninger, David, Florida Atlantic University
Abstract/Description: Oxidative damage is an inevitable consequence of aerobic respiration. Methionine sulfoxide reductases (Msr) are a group of enzymes that function to repair oxidized methionine residues in both free methionine and methionine in proteins. MsrA was the first of these enzymes to be discovered and is the most thoroughly studied. It is thought to play a role in both the aging process and probably several neurodegenerative diseases. I recently obtained a strain of Drosophila that was reported to have...
Show moreOxidative damage is an inevitable consequence of aerobic respiration. Methionine sulfoxide reductases (Msr) are a group of enzymes that function to repair oxidized methionine residues in both free methionine and methionine in proteins. MsrA was the first of these enzymes to be discovered and is the most thoroughly studied. It is thought to play a role in both the aging process and probably several neurodegenerative diseases. I recently obtained a strain of Drosophila that was reported to have a P-element transposon located within Exon 2 (part of the open reading frame) of the eip71cd gene, which is the Drosophila homolog of MsrA. Thus, the transposon insertion should disrupt expression of the msrA gene. I did a series of experiments to "jump out" the P-element in an effort to recover two types of isogenic strains. The first would be a null mutation of the MsrA gene created by deletion of flanking genomic DNA when the P-element excised from the chromosome. The second would be a precise excision of the P-element, which would restore the genetic locus to its original structure. This study looks at the effect of a null mutant of the MsrA gene on aging and resistance to oxidative stress.
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Date Issued: 2006
PURL: http://purl.flvc.org/fau/fd/FA00000772
Subject Headings: Genetic regulation, Oxidation-reduction reaction, Antioxidants, Oxygen--Physiological effect, Proteins--Chemical modification
Format: Document (PDF)

Title: Methionine sulfoxide reductase (Msr) deficiency leads to a reduction of dopamine levels in Drosophila.
Creator: Hernandez, Caesar, Binninger, David, Weissbach, Herbert, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Biological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological...
Show moreBiological homeostasis relies on protective mechanisms that respond to cellular oxidation caused primarily by free radical reactions. Methionine sulfoxide reductases (Msr) are a class of enzymes that reverse oxidative damage to methionine in proteins. The focus of this study is on the relationship between Msr and dopamine levels in Drosophila. Dopaminergic neurons in Drosophila have comparable roles to those found in humans. A deficit in dopamine leads to the onset of many neurological disorders including the loss of fine motor control—a neurodegenerative condition characteristic of Parkinson’s disease (PD). We found that dopamine levels in the heads of MsrAΔ/ΔBΔ/Δ mutants are significantly reduced in comparison to MsrA ⁺/⁺ B⁺/⁺ heads. In addition, wefound protein and expression levels are markedly reduced in an Msr-deficient system. Our findings suggest an important role for the Msr system in the CNS.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004202, http://purl.flvc.org/fau/fd/FA00004202
Subject Headings: Cellular signal transduction, Dopamine -- Receptors, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Proteins -- Chemical modification
Format: Document (PDF)

Title: Methionine sulfoxide reductase A (MsrA) and aging in the anoxia-tolerant freshwater turtle (Trachemys scripta).
Creator: Bruce, Lynsey Erin., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: The enzyme Methionine sulfoxide reductase A (MsrA) repairs oxidized proteins, and may act as a scavenger of reactive oxygen species (ROS), making it a potential therapeutic target for age-related neurodegenerative diseases. The anoxia-tolerant turtle offers a unique model to observe the effects of oxidative stress on a system that maintains neuronal function following anoxia and reoxygenation, and that ages without senescence. MsrA is present in both the mitochondria and cytosol, with protein...
Show moreThe enzyme Methionine sulfoxide reductase A (MsrA) repairs oxidized proteins, and may act as a scavenger of reactive oxygen species (ROS), making it a potential therapeutic target for age-related neurodegenerative diseases. The anoxia-tolerant turtle offers a unique model to observe the effects of oxidative stress on a system that maintains neuronal function following anoxia and reoxygenation, and that ages without senescence. MsrA is present in both the mitochondria and cytosol, with protein levels increasing respectively 3- and 4-fold over 4 hours of anoxia, and remaining 2-fold higher than basal upon reoxygenation. MsrA was knocked down in neuronally-enriched cell cultures via RNAi transfection. Propidium iodide staining showed no significant cell death during anoxia, but this increased 7-fold upon reoxygenation, suggesting a role for MsrA in ROS suppression during reperfusion. This is the first report in any system of MsrA transcript and protein levels being regulated by oxygen levels.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2683139
Subject Headings: Oxidation-reduction reaction, Proteins, Chemical modification, Turtles, Physiology, Oxygen, Physiological effect, Aging, Molecular aspects
Format: Document (PDF)

Title: Molecular and phenotypic characterization of MsrA MsrB mutants of Drosophila melanogaster.
Creator: Robbins, Kelli., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Aging is a multifactoral biological process of progressive and deleterious changes partially attributed to a build up of oxidatively damaged biomolecules resulting from attacks by free radicals. Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine (Met) residues found in proteins. Oxidized Met produces two enantiomers, Met-S-(o) and Met-R-(o), reduced by MsrA and MsrB respectively. Unlike other model organisms, our MsrA null fly mutant did not display increased...
Show moreAging is a multifactoral biological process of progressive and deleterious changes partially attributed to a build up of oxidatively damaged biomolecules resulting from attacks by free radicals. Methionine sulfoxide reductases (Msrs) are enzymes that repair oxidized methionine (Met) residues found in proteins. Oxidized Met produces two enantiomers, Met-S-(o) and Met-R-(o), reduced by MsrA and MsrB respectively. Unlike other model organisms, our MsrA null fly mutant did not display increased sensitivity to oxidative stress or shortened lifespan, suggesting that in Drosophila, having either a functional copy of either Msr is sufficient. Here, two Msr mutant types were phenotypically assayed against isogenic controls. Results suggest that only the loss of both MsrA and MsrB produces increased sensitivity to oxidative stress and shortened lifespan, while locomotor defects became more severe with the full Msr knockout fly.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/359920
Subject Headings: Genetic regulation, Oxidation-reduction reaction, Proteins, Chemical modification, Aging, Molecular aspects, Mutation (Biology), Cell metabolism, Mitochondrial DNA
Format: Document (PDF)

Title: Studies on the mechanism by which sulindac sensitizes cancer cells to oxidative stress.
Creator: Kreymerman, Alexander, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Sulindac is a known NSAID that has also been shown to have anti-cancer activity that is not related to its ability to inhibit COX 1 and 2. During the past 15 years there have been a large number of studies attempting to elucidate its mechanism of action. Our laboratory has shown that sulindac can both protect normal cells and enhance the killing of cancer cells under oxidative stress from H2O2 and TBHP. However, except for mitochondrial dysfunction and ROS production, the mechanism by which...
Show moreSulindac is a known NSAID that has also been shown to have anti-cancer activity that is not related to its ability to inhibit COX 1 and 2. During the past 15 years there have been a large number of studies attempting to elucidate its mechanism of action. Our laboratory has shown that sulindac can both protect normal cells and enhance the killing of cancer cells under oxidative stress from H2O2 and TBHP. However, except for mitochondrial dysfunction and ROS production, the mechanism by which sulindac sensitized the cancer cells to oxidative stress remains unknown. Results of this research project suggest that the effect of sulindac and oxidative stress not only involves mitochondrial ROS production, but also aspects of the preconditioning response. In normal cells this leads to survival by a preconditioning pathway, likely involving PKCε. . However, cancer cells react by initiating a pathway leading to apoptosis involving PKCδ.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3183124
Subject Headings: Proteins, Chemical modification, Cellular signal transduction, Biochemical markers, Diagnostic use, Drug resistance in cancer cells, Oxidation-reduction reaction
Format: Document (PDF)

Title: Role of methionine sulfoxide reductase in thermal-induced spreading depression coma in Drosophila melanogaster.
Creator: Schey, Karin., Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Drosophila melanogaster encounter periods of increased temperature or decreased oxygen in its native environment. One consequence of these environmental stresses is increased production of reactive oxygen species that damage major molecules within cells. Another consequence is that flies fall into a protective coma where biological functions are minimized to conserve energy expenditures. This biological phenomenon is called spreading depression. The overarching aim of this project is to...
Show moreDrosophila melanogaster encounter periods of increased temperature or decreased oxygen in its native environment. One consequence of these environmental stresses is increased production of reactive oxygen species that damage major molecules within cells. Another consequence is that flies fall into a protective coma where biological functions are minimized to conserve energy expenditures. This biological phenomenon is called spreading depression. The overarching aim of this project is to determine if methionine sulfoxide reductases affect entrance or exit from the protective coma induced by acute thermal stress. The data revealed that complete deficiency of Msr in young flies causes a faster induction of the coma. In both young and old flies, Msr does not affect average recovery time but does affect the pattern of recovery from coma. Entrance into the coma is age dependent with young flies maintaining activity longer than before entering into the coma as compared to old flies.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3355873
Subject Headings: Cellular signal transduction, Proteins, Chemical modification, Spreading cortical depression, Oxidation-reduction reaction, Aging, Molecular aspects, Mutation (Biology)
Format: Document (PDF)

Title: Methionine sulfoxide reductase (MSR) modulates lifespan andLocomotion in drosophila melanogaster.
Creator: Bruce, Lindsay, Binninger, David, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description: Oxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in...
Show moreOxidative stress is considered a major factor in the etiology of age related diseases and the aging process itself. Organisms have developed mechanisms to protect against oxidative damage resulting from increased production of reactive oxygen species during aging. One of the major antioxidant systems is the methionine sulfoxide reductase (Msr) enzyme family. The two major Msr enzymes, MsrA and MsrB, can stereospecifically reduce the S and R epimers, respectively, of methionine sulfoxide in proteins back to methionine. This study, using Drosophila melanogaster, decribes the first animal system lacking both MsrA and MsrB. The loss of either MsrA or MsrB had no effect on lifespan in Drosophila, but loss of MsrB results in a slight decrease in locomotor activity from middle age onward. Double mutants lacking both forms of Msr have a significantly decreased lifespan and decreased locomotor activity at all ages examined. The double Msr mutants had no detectable increase in protein oxidation or decrease in mitochondrial function and were not more sensitive to oxidative stress. These results suggested that other cellular antioxidant systems were protecting the flies against oxidative damage and the decreased life span observed in the double knockouts was not due to widespread oxidative damage. However, one cannot exclude limited oxidative damage to a specific locus or cell type. In this regard, it was observed that older animals, lacking both MsrA and MsrB, have significantly reduced levels of dopamine, suggesting there might be oxidative damage to the dopaminergic neurons. Preliminary results also suggest that the ratio of F to G actin is skewed towards G actin in all mutants. The present results could have relevance to the loss of dopaminergic neurons in Parkinson’s disease.
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Date Issued: 2015
PURL: http://purl.flvc.org/fau/fd/FA00004431, http://purl.flvc.org/fau/fd/FA00004431
Subject Headings: Aging -- Molecular aspects, Cellular signal transduction, Drosophila melanogaster -- Genetics, Mitochondrial pathology, Mutation (Biology), Oxidative stress, Proteins -- Chemical modification
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)

Chemical modification (7)	+ -
Oxidation-reduction reaction (7)	+ -
Proteins (7)	+ -
Cellular signal transduction (6)	+ -
Genetic regulation (5)	+ -

Mutation (Biology) (4)	+ -
Aging (3)	+ -
Mitochondrial pathology (3)	+ -
Molecular aspects (3)	+ -
Proteins -- Chemical modification (3)	+ -
Proteins--Chemical modification (3)	+ -
Antioxidants (2)	+ -
Biochemical markers (2)	+ -
Oxygen (2)	+ -
Physiological effect (2)	+ -
Physiology (2)	+ -
Turtles (2)	+ -
Aging -- Molecular aspects (1)	+ -
Aging--Molecular aspects. (1)	+ -
Anoxemia (1)	+ -
Cell metabolism (1)	+ -
Cellular signal transduction. (1)	+ -
Diagnostic use (1)	+ -
Dopamine -- Receptors (1)	+ -
Drosophila melanogaster -- Genetics (1)	+ -
Drosophila melanogaster -- Life cycles (1)	+ -
Drosophila melanogaster--Genetics. (1)	+ -
Drosophila melanogaster -- Genetics (1)	+ -
Drug resistance in cancer cells (1)	+ -
Eye--Physiology (1)	+ -

Charles E. Schmidt College of Science (12)	+ -
Department of Biological Sciences (11)	+ -
Florida Atlantic University (7)	+ -
Binninger, David (4)	+ -
Bruce, Lindsay (1)	+ -

Bruce, Lynsey Erin. (1)	+ -
Brunell, David J. (1)	+ -
Caplan, Stacee Lee (1)	+ -
Dawson-Scully, Ken (1)	+ -
Department of Biomedical Science (1)	+ -
Ding, Di (1)	+ -
Foss, Katie (1)	+ -
Hernandez, Caesar (1)	+ -
Kantorow, Marc (1)	+ -
Kesaraju, Shailaja. (1)	+ -
Kreymerman, Alexander (1)	+ -
Lee, Wanda (1)	+ -
Milton, Sarah L. (1)	+ -
Robbins, Kelli. (1)	+ -
Schey, Karin. (1)	+ -
Singkornrat, Diana (1)	+ -
Verriotto, Jennifer. (1)	+ -
Weissbach, Herbert (1)	+ -
Zhang, Xing-Hai (1)	+ -

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