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1
Knight, Simon Alexander Bowles 1961. "The use of anti-glutathione peroxidase antibodies in the study of selenium-dependent glutathione peroxidase." Thesis, The University of Arizona, 1988. http://hdl.handle.net/10150/276906.
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Liver glutathione peroxidase activity is affected by changes in selenium (Se) status. To investigate the effect of Se status on GSH-Px protein we prepared antibodies against rat liver GSH-Px and used them in an ELISA. The immunoreactivity of the anti-GSH-Px antibodies against GSH-Px was both tissue and species specific. When rats were depleted of Se, liver GSH-Px activity decreased exponentially to zero with a half-life of 2.8 d. Liver GSH-Px protein also decreased exponentially, but not to zero, with a longer half-life of 5.2 d. Dietary repletion of Se-deficient rats with 0.5 mg Se/kg diet increased GSH-Px protein and activity after 1 d. After 14 d of repletion the levels of GSH-Px protein and activity had plateaued at the levels present in Se-adequate rats. When Se-deficient rats were injected with 15 or 60 ug Se, only rats injected with 60 ug Se and killed 24 h later showed an increase in GSH-Px protein and activity. These results suggest that when Se is limiting, GSH-Px protein and GSH-Px activity are coordinately regulated by the available Se, but in Se-adequacy homeostatic processes control the level of GSH-Px.
2
Ufer, Christoph. "Untersuchungen zur Expressionsregulation der Phospholipid-Hydroperoxid-Glutathion-Peroxidase." Doctoral thesis, [S.l.] : [s.n.], 2006. http://deposit.ddb.de/cgi-bin/dokserv?idn=979803632.
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Saudrais, Élodie. "Mécanismes de neuroprotection liés au glutathion dans la barrière sang - liquide céphalorachidien choroïdienne au cours du développement périnatal." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1026/document.
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Plus de 50 % des handicaps neurodéveloppementaux sont dus à une exposition périnatale à des stress toxiques ou oxydants. Comprendre comment le cerveau est protégé au cours du développement périnatal et pourquoi ses mécanismes de défense sont dépassés lorsque l’enfant est soumis à un stress important est donc crucial. La barrière sang – liquide céphalorachidien (LCR), localisée au niveau des plexus choroïdes, présente une capacité de détoxification élevée et pourrait donc avoir un rôle prépondérant dans la protection du cerveau au stade périnatal. Nous avons étudié la capacité de plusieurs enzymes choroïdiennes à protéger l'environnement liquidien cérébral pendant la période postnatale chez le rat, et évalué si leurs activités pouvaient être induites par la voie du nuclear factor erythroid-2-related factor 2 (Nrf2). Le facteur Nrf2 peut en effet moduler l’expression de différents gènes codant pour des enzymes de détoxification. Nous avons montré que les glutathion transférases (Gst) et les glutathion peroxydases (Gpx), intervenant respectivement dans l’inactivation des molécules toxiques et dans la régulation du stress oxydant, présentaient des activités choroïdiennes élevées pendant la période postnatale, et avons caractérisé fonctionnellement leur capacités de neuroprotection. Le traitement des ratons avec du diméthylfumarate (DMF), inducteur de la voie Nrf2, induit la migration nucléaire de Nrf2, augmente l’activité choroïdienne Gst, et réduit de 40 % le passage cérébral de toxiques substrats des Gst. Ces données montrent la capacité neuroprotectrice précoce des plexus choroïdes, et indique qu’elle peut être induite pharmacologiquementMore than 50 % of intellectual or sensory-motor deficits in children are due to perinatal exposure to oxidative stress or toxicants. Understanding brain protection mechanisms during development is crucial to design therapeutic strategies to address these disabilitating disorders. The choroid plexuses, forming an interface between the blood and the cerebrospinal fluid (CSF), have a high detoxifying capacity, suggesting their involvement in neuroprotection. The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway can modulate the expression of several genes encoding for antioxidant proteins and detoxifying enzymes. We studied the ability of several choroidal enzyme families to protect the brain fluid environment during the postnatal period in rat and explored whether this protection can be enhanced by Nrf2 pathway. We focused on glutathione transferases (Gsts), which conjugate toxic compounds to glutathione, and glutathione peroxidases (Gpxs), which detoxify reactive oxygen species. Gst and Gpx specific activities were high during the postnatal period in choroid plexuses compared to the cerebral cortex, and their neuroprotective functions were efficient. The Nrf2 factor is expressed in choroid plexuses during the perinatal period. Treatment of rat pups with Nrf2 activator dimethylfumarate induced Nrf2 nuclear translocation and increased Gst activities in choroid plexus tissues. The dimethylfumarate treatment resulted in a large decrease of the blood-to-CSF permeability of a prototypical Gst substrate. These data substantiate the early neuroprotective functions of choroid plexuses, which can be enhanced upon treatment with clinically used pharmacological compounds
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Adams, Ruqaiyah. "Characterization of a novel soybean candidate glutathione peroxidase/thioredoxin-dependent peroxidase under salt stress." Thesis, University of the Western Cape, 2012. http://hdl.handle.net/11394/3800.
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The study aimed to investigate the following:
1. Investigate a putative glutathione peroxidase gene (Glyma17g34110) within Glycine max by an in silico analysis and spatial expression.
2. Determine the effects of exogenously applied nitric oxide on the expression of
Glyma17g34110.
3. Investigate the antioxidant mechanism with attention to Glyma17g34110,reactive
oxygen species and cell death in the response to salt stress.
4. Establish whether Glyma17g34110 is a glutathione peroxidase or thioredoxindependent
peroxidase gene.Magister Scientiae - MSc
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Wiencierz, Anne Maria. "Entwicklung eines Dual-Luciferase-Reportergen-Assays zum Nachweis der Induktion antioxidativer Enzyme durch Nahrungsbestandteile." Master's thesis, Universität Potsdam, 2008. http://opus.kobv.de/ubp/volltexte/2009/2790/.
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Die Induktion antioxidativer Enzyme gilt als eine Möglichkeit, die antioxidative Kapazität von Zellen zu steigern und dadurch mit oxidativem Stress assoziierten Erkrankungen (z. B. Herz-Kreislauf-Erkrankungen, Neurodegeneration, Atherosklerose) vorzubeugen. Ausgehend davon wurde in der vorliegenden Arbeit der Dual-Luciferase-Reportergen-(DLR)-Assay zum Nachweis der Induktion der antioxidativen Enzyme Katalase (CAT), zytosolische Glutathion-Peroxidase (GPX1) und Kupfer-Zink-Superoxid-Dismutase (SOD1) entwickelt. Im Zuge dessen wurden drei Säugetierzelllinien (CaCo2, IEC-18, V79) auf ihre Eignung zur Modellzelllinie untersucht. Aufgrund der Transfektionseffizienz wurde die Fibroblastenzelllinie V79 ausgewählt. Zur Gewährleistung eines hohen Substanzdurchsatzes des DLR-Assays wurden bei der Etablierung Parameter wie Kulturplattenformat, DNA-Menge, Luciferasen-Kinetik berücksichtigt.
Nach erfolgreicher Etablierung des Versuchs im 96-Well-Format wurden L-Carnitin, Catechin, Epigallocatechingallat, Genistein, Wasserstoffperoxid (H2O2), Natrium-Ascorbat, Paraquat, Quercetin, 12-O-Tetradecanoylphorbol-13-Acetat (TPA) und Trolox in nicht-zytotoxischen Konzentrationen hinsichtlich der Aktivierung des Ratten-CAT-, des humanen GPX1- und des humanen SOD1-Promotors untersucht. Die Bestimmung der maximal tolerierbaren Behandlungskonzentration erfolgte im Vorfeld mittels Resazurintest.
Von den zehn Verbindungen zeichneten sich drei Substanzen als potente Induktoren für die SOD1 und die GPX1 aus. Die 24-stündige Behandlung von mit Reportergenkonstrukten transient transfizierten V79-Zellen mit 100 µM Paraquat resultierte in einer Verdopplung der relativen SOD1-Promotor-Aktivität und einer Erhöhung der relativen GPX1-Promotor-Aktivität auf 1,6 bzw. 1,7. Die Stimulation mit 20 µM Genistein oder 10 µM Quercetin führte wiederum zu einer Verdopplung bis Verdreifachung der relativen SOD1- und GPX1-Promotor-Aktivität. Der Promotor der Rattenkatalase konnte demgegenüber nur durch 50 µM H2O2 aktiviert werden (1,5fach).
Für diesen DLR-Assays bieten sich folglich Genistein, Quercetin wie auch H2O2 als Referenzsubstanzen an. Um aber eine qualitative Charakterisierung der einzelnen Verbindungen hinsichtlich ihres Induktionspotentials zu gewährleisten, sollten von allen getesteten Substanzen Dosis-Wirkungskurven aufgenommen werden. Zudem wird für den routinemäßigen Einsatz die Verwendung stabil transfizierter Zellen zur Vermeidung von mit der Transfektion verbundenen experimentellen Schwankungen empfohlen.The induction of antioxidative enzymes might be an opportunity to elevate the cellular antioxidative capacity and, thus, to prevent oxidative stress associated diseases (e. g. cardio-vascular disease, neurodegenerative disease, atherosclerosis). Based on this idea the dual luciferase reporter gene (DLR) assay was developed to demonstrate the induction of three antioxidative enzymes: catalase (CAT), cytosolic glutathione peroxidase (GPX1), and copper-zinc superoxide dismutase (SOD1). In the course of the development three mammalian cell lines (CaCo2, IEC-18, V79) were tested for their ability to serve as a model cell line. The line V79 was chosen due to the transfection efficiency. To give consideration to a high-throughput several parameters were studied (e. g. format of the cultural plates, amount of DNA, kinetics of the luciferases) and the DLR assay was successfully established in 96 well plates. Subsequently, L-carnitine, catechin, epigallocatechin gallate, genistein, hydrogen peroxide (H2O2), sodium ascorbate, paraquat, quercetin, 12-O-tetradecanoylphorbol-13-acetate (TPA) and trolox were tested in non-cytotoxic concentrations for the activation of the rat CAT, human GPX1 and human SOD1 promoter. The maximally tolerable concentrations were determined by resazurin test in advance. Three out of these ten compounds were identified as potent inducers of GPX1 and SOD1. Stimulation of reporter gene construct transient transfected V79 cells for 24 hours with 100 µM paraquat caused a duplication of the relative GPX1 promoter activity and a 1.6-/1.7-fold increase of the relative SOD1 promoter activity. The incubation with 20 µM gen-istein or 10 µM quercetin resulted in duplication to triplication of both, the relative GPX1 and SOD1 promoter activity. In contrast, the rat CAT promoter was activated by 50 µM H2O2 (1.5-fold). Consequently, genistein, quercetin, and H2O2 are considered to be suitable reference substances for this DLR assay. To further characterize the inducing potential of the tested compounds all of them should be tested in different concentrations. Furthermore, for the routinely performed DLR assay it is recommended to use stably transfected cells to eliminate transfection caused variations.
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De, Oliveira Bouvière Jessica. "Rôle de la sélénoprotéine P et de la glutathion peroxydase 3 dans le phénotype des macrophages et la régénération musculaire." Thesis, Lyon, 2019. http://www.theses.fr/2019LYSE1167/document.
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Les macrophages peuvent transiter entre les états pro et anti-inflammatoires, un processus appelé de polarisation. Les molécules sécrétées par les macrophages sont capables d'induire différents profils métaboliques. Les analyses transcriptomiques de macrophages pro et anti-inflammatoires humains ont identifié nouvelles molécules avec un peptide sécrétoire. Parmi ces candidates, les sélénoprotéines étaient l’une des plus exprimés dans les macrophages anti-inflammatoires. Ainsi, nous évaluons l’impact des sélénoprotéines sur la polarisation des macrophages, secondaires à l’inflammation et leur implication au cours de la régénération musculaire. Une fois établi que les cytokines stimulent les transitions des macrophages, nous avons utilisé IFN-gamma et IL10 pour explorer ces différents profils inflammatoires in vitro. Les macrophages dérivés de la moelle osseuse de WT et de sélénoprotéines KO ont été polarisés avec les deux cytokines pour obtenir un phénotype pro et anti-inflammatoire, respectivement. Nos résultats ont montré que, en absence de sélénoprotéines, les macrophages réduisaient leur capacité à migrer d'un état d'activation à l’autre par rapport au contrôle, soulignant ainsi l'importance de ces molécules pour contrôler les états d’alternance des macrophages. Le modèle de lésion en réponse à la cardiotoxine a été utilisé pour examiner, in vivo, la capacité des macrophages à modifier leur phénotype au cours de la régénération du muscle squelettique. Trois jours après une lésion, la population pro est remplacé par une anti-inflammatoire, comme l'a déjà montré l'analyse par cytométrie en flux. Cependant, les modèles de macrophages pro-inflammatoires sélénoprotéines KO étaient présent trois fois plus nombreux relativement à la population anti-inflammatoire, indiquant que ces macrophages n’ont pas acquis le phénotype anti-inflammatoire. De plus, nous évaluons la fonction des macrophages en absence de sélénoprotéines. Suite à la polarisation avec les cytokines, décrites ci-dessus, les expériences ont démontré que les macrophages anti-inflammatoires WT favorisaient la fusion des myoblastes, alors que les sélénoprotéines KO n'étaient pas en mesure de maintenir cette fusion. En conclusion, les sélénoprotéines modulent la polarisation des macrophages, impliquant leur capacité à acquérir différents phénotypes in vitro et in vivo, ainsi que leurs effets sur la fusion des myoblastesMacrophages can go through transitions between pro and anti-inflammatory states, one process called polarization skewing. Molecules secreted by macrophages are able to induce different metabolic profiles. Transcriptomic analyses of human pro and anti-inflammatory macrophages identified new molecules with a secretory peptide. Selenoproteins were one of the most expressed in anti-inflammatory macrophages. Thus, we evaluate the respective roles of selenoproteins on macrophage polarization parameters in inflammation and their implication in regenerative processes. Once established that cytokines largely spur macrophage transitions we used IFN-gamma and IL10 to explore these different inflammatory profiles in vitro. Bone marrow derived macrophages from WT and selenoproteins KO models were polarized with both cytokines to obtain a pro and anti-inflammatory phenotype, respectively. Our results showed that without selenoproteins, macrophages had impairment of their capacity to switch from one activation state to another as compared with the control, emphasizing the importance of these molecules to control macrophage transitional states. The cardiotoxin injury model was use to in vivo examine the macrophages capability to switch their phenotype during skeletal muscle regeneration. Three days after an injury pro is replaced by anti-inflammatory population, as has already been shown by flow cytometry analysis. However, macrophages from selenoproteins KO presented three-fold increase of pro-inflammatory macrophages while anti-inflammatory population decreased, indicating that they did not acquire an anti-inflammatory phenotype. In addition, we evaluate the macrophage function in absence of selenoproteins. After polarization with cytokines, experiments demonstrated that WT anti-inflammatory macrophages promoted myoblast fusion, whereas selenoproteins KO were not able to sustain their fusion. In conclusion, selenoproteins modulate macrophage polarization implicating their ability to acquire different phenotypes in vitro and in vivo as well as their effects on myoblast fusion
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Hille, Jan Matthias. "Die Trinukleotid-Expansion des Gens für zelluläre Glutathion-Peroxidase bei Patienten mit sporadischer amyotropher Lateralsklerose." Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2003. http://dx.doi.org/10.18452/14952.
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Trotz intensiver Forschung ist die Ätiologie der sporadischen amyotrophen Lateralsklerose (sALS) weiterhin unbekannt. Zahlreiche Anzeichen deuten allerdings auf eine Mitbeteiligung von oxidativem Streß an der Pathogenese der sALS hin. So fand sich eine verminderte Aktivität der zellulären Glutathion-Peroxidase (GPX-1), eines als Radikalenfänger fungierenden Enzyms, in den Gyrus praecentrales bei sALS-Patienten. Zusätzliche Studien fanden eine Trinukleotid-Expansion des GGG-repeats im 1. Exon des für die GPX-1 kodierenden Gens. Da Trinukleotid-Expansionen bei einer Vielzahl von neurodegenerativen Erkrankungen wie dem Kennedy-Syndrom und der spinozerebellären Ataxie nachgewiesen werden konnten, war das Ziel dieser Arbeit, eine fragliche Mitbeteiligung dieser Trinkukleotid-Expansion der GPX-1 an der Pathogenese der sALS zu klären. Nach Etablierung der Methode bestehend aus einer Kombination von Polymerase-Kettenreaktion (PCR) und Restriktions-Fragment-Längen-Polymorphismus (RFLP) zeigte sich, dass der Genotyp 4*5 bei einer Gruppe von 231 sALS-Patienten signifikant häufiger vertreten war, wohingegen der Genotyp 5*6 in der Kontrollgruppe signifikant überrepräsentiert war. Im Vergleich zu bisher veröffentlichten Ergebnissen ließ sich der Genotyp 4*4 in der Kontrollgruppe signifikant häufiger nachweisen. Ursache hierfür könnte - neben einem tatsächlich erhöhten Risiko, an sALS zu erkranken - der Zusammenhang mit einem C/T-Polymorphismus der GPX-1 sein, der zu einem Austausch von Prolin zu Leucin führt. Die für Leucin kodierende Variante tritt hierbei nur zusammen mit 5 GCG-repeats auf, während die für Prolin kodierende Variante mit dem Auftreten von 4 und 6 GCG-repeats korreliert.In spite of intensive research efforts the ethiology of sporadic amyotrophic lateral sclerosis (sALS) remains unknown. Various indices indeed suggest an involvement of oxidative stress in the pathogenesis of sALS. Thus a decreased activity of the cellular glutathione peroxidase (GPX-1) in gyrus praecentrales of sALS patients could be detected, an enzym strongly participating in the clearence of free radicals. Additional studies uncovered a trinucleotid expansion of a GCG repeat in the 1st exon of the gene coding for GPX-1. Such trinucleotid expansions play a major role in a variety of neurodegenerative disorders like the Kennedy Syndrom and spinal-cerebellary ataxia. Goal of this work was to disclose a possible involvement of the GCG expansion in the pathogenesis of sALS. Through the successful establishment of the methodology consisting of a combination of polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) we could demonstrate a significant decrease of the genotype 4*5 in a group of 231 sALS patients, whereas the genotype 5*6 was overrepresented in the control group. Compared to hitherto publications we detected an increased occurrence of the 4*4 genotype in the control group. Besides an effective increased risk to contract sALS, the distribution of the GCG-repeat expansion could originate from another C/T polymorphism of GPX-1-gene leading to a substitution of proline with leucine. The leucine coding mutation occurs together with 5 GCG repeats, whereas the proline coding mutant correlates with 4 and 6 GCG-repeats.
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Huang, Wenhu. "Extracellular glutathione peroxidase purification, immunoassay, nutritional regulation and clinical aspects /." Lund : Lund University Dept. of Applied Nutrition and Food Chemistry, 1996. http://catalog.hathitrust.org/api/volumes/oclc/38100668.html.
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Eftekharpour, Eftekhar. "Glutathione dependent and thioredoxin dependent peroxidase systems in neural cells." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ63863.pdf.
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Phillips, Kyle. "Characterisation of a novel soybean candidate glutathione peroxidase/thioredoxin-dependent peroxidase in soybean exposed to osmotic/drought stress." University of the Western Cape, 2012. http://hdl.handle.net/11394/4643.
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>Magister Scientiae - MScDrought stress is a major contributor to reduced soybean crop yield and quality, this can however be mitigated by the plant’s antioxidant defence mechanisms. One group of antioxidant enzymes that are active in these defence mechanisms are glutathione peroxidases (GPXs). GPXs are antioxidant proteins which are able to reduce H2O2, a toxic reactive oxygen species which accumulates under stress conditions. This study aims at isolating the protein encoded by Glyma01g42840 and determining if it has Phospholipid hydroperoxidase glutathione peroxidase (PHGPX) and/or Thioredoxin dependent peroxidase (TRX-PX) activity as well as assaying the effect of Drought stress on the expression of this putative GPX . This will be accomplished by molecular cloning, sequencing as well as the expression of the isolated protein to assay it enzymatic activity. It was found that the enzyme encoded by Glyma01g42840 is able to use glutathione and thioredoxin as electron donors for the detoxification peroxides, however enzymatic activity is more efficient when using glutathione as an electron donor. In conclusion it was found that glyma01g42840 encodes an enzyme which is able to utilise more than one electron donor and as glutathione produces the greatest amount of enzymatic activity it can be said that glyma01g42840 encodes a GPX.
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Schneider, Manuela. "Untersuchungen zur Funktion der Phospholipid-Hydroperoxid-Glutathion-Peroxidase anhand eines Knock-out-Mausmodells." Diss., kostenfrei, 2006. http://edoc.ub.uni-muenchen.de/8128/.
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Grünler, Nadine. "Untersuchungen zur Rolle der Glutathion-Peroxidase 4 als möglicher Redox-Sensor in Säugetierzellen." Diss., Ludwig-Maximilians-Universität München, 2015. http://nbn-resolving.de/urn:nbn:de:bvb:19-182722.
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GPx4 besitzt vielfältige Funktionen im Redox-Metabolismus von Zellen. Ursprünglich wurde sie als ein Enzym beschrieben, das hoch effizient Phospholipidhydroperoxide zu den entsprechenden Alkoholen unter GSH-Verbrauch reduzieren kann. Weiterhin hatte sich in den letzten 10 bis 15 Jahren gezeigt, dass sie eine essenzielle Rolle als Thiolperoxidase in der Spermienreifung ausübt. Eine weitere Funktion stellt möglicherweise die eines Redox-Sensors dar, der auf die Änderung des zellulären Redox-Milieus mit der Aktivierung von antioxidativen Zellsignalwegen reagiert. Diese Funktion konnte bislang nur für das GPx4-Homolog in der Hefe nachgewiesen werden und kann aufgrund der Rolle, die die GPx4 bei der Spermienreifung in Mäusen spielt, auch für Säugetiere postuliert werden. Es handelt sich dabei um die Fähigkeit der GPx4 in ihrer Funktion als Thiolperoxidase Disulfid- oder auch Selenylsulfidbindungen zwischen anderen Proteinen zu bilden. Dabei ist die GPx4 vermutlich auch in der Lage, ihre eigenen Cysteine als Substrat zu akzeptieren, was allerdings im Falle der Spermienreifung zu einer Inaktivierung der peroxidativen Funktion führt. Diese Thiolperoxidasefunktion ist abhängig von der Menge an freiem GSH.
Der Schwerpunkt dieser Arbeit war es, mögliche Interaktionspartner in somatischen Zellen zu identifizieren, wobei die Thiolperoxidasefunktion der GPx4 bei Änderung des zellulären Redox-Milieus in Form von oxidativem Stress ausgenutzt werden sollte.
Als Methode wählten wir ein modifiziertes Tandem-Affinity-Purification-enhanced-Verfahren (TAPe). Mit Hilfe dessen wurde eine mit einem Strep/Flag-Tag versehene GPx4 oder verschiedene Mutanten stabil in induzierbaren GPx4 Knockout murinen embryonalen Fibroblasten exprimiert, sodass die getaggte GPx4 mittels des TAPe Verfahren aus den Zellen aufgereinigt werden konnte. Um intrazelluläre GSH-Konzentrationen zu reduzieren und die GPx4 zu oxidieren, wurden die Zellen vor der Lyse mit BSO und tBOOH vorbehandelt. Die Eluate aus diesen Aufreinigungen wurden anschließend anhand der Massenspektrometrie, Silberfärbung und Western Blots analysiert.
Es ließen sich eine ganze Reihe von Proteinen identifizieren, die ebenfalls eine wichtige Rolle in der Aufrechterhaltung des intrazellulären Redox-Milieus spielen und an der Regulierung von Zellsignalwegen beteiligt sind. Nach den bisherigen Analysen bedarf es aber noch einer Bestätigung mittels co-Immunpräzipitation und Immunoblot-Analysen. Besonders aktuelle Erkenntnisse, die neue Zelltodsignalwege, wie zum Beispiel die Ferroptose, analysieren, stellen eine interessante und äußerst relevante Richtung für zukünftige Projekte in der Erforschung der GPx4 und ihrer Rolle als Redox-Sensor und Regulator von Zelltodsignalwegen dar.
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Ezea, Patience Cole. "A study of glutathione peroxidase 4 function in human intestinal epithelial cells." Thesis, University of Newcastle Upon Tyne, 2013. http://hdl.handle.net/10443/1823.
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Intake of the micronutrient selenium, which is incorporated into selenoproteins in humans, has been implicated in affecting risk of colorectal cancer. A genetic variant in the gene encoding the selenoprotein glutathione peroxidase 4 (GPx4) has been reported to influence colorectal cancer risk. In this study the role of GPx4 was investigated in the Caco-2 intestinal cell line using RNA silencing. GPX4 expression was knocked–down by ~60% and an unbiased gene microarray analysis of the total Caco-2 cell transcriptome was carried out using Illumina HumanHT-12v3 beadchips. The data were validated by real-time PCR. Ingenuity Pathway analysis showed that the major canonical pathways affected by GPX4 knock-down were oxidative phosphorylation, ubiquinone biosynthesis and mitochondrial dysfunction and the top two toxicological lists were mitochondrial dysfunction and oxidative stress. Western blotting and real-time PCR confirmed that knock-down affected target genes encoding components of respiratory complexes I, IV and V as well as the protein apoptosis-inducing factor (AIF). GPX4 knock-down increased levels of mitochondrial reactive oxygen species and oxidised lipid, and decreased mitochondrial adenosine triphosphate (ATP) levels and mitochondrial membrane potential. Time course experiments showed changes in AIF expression preceded those in the respiratory complexes. GPX4 knock-down increased apoptosis and changed protein expression of Caspase-9, Bax and Bcl-2. Treatment of cells with the antioxidant mitoquinone prevented the effects of GPX4 knockdown on mitochondrial reactive oxygen species, oxidised lipid and mitochondrial membrane potential but not the effect on AIF. These data suggest that in intestinal epithelial cells GPx4, through effects on lipid peroxidation and AIF, plays a complex role in maintaining the oxidative phosphorylation system and protecting mitochondria from oxidative damage and apoptosis.
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Bao, Yongping. "A study of the role of the selenoenzyme : phospholipid hydroperoxide glutathione peroxidase." Thesis, University of East Anglia, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317979.
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Wen, Wu. "UGA-mediated selenium incorporation into glutathione peroxidase 1 and green fluorescent protein /." free to MU campus, to others for purchase, 1998. http://wwwlib.umi.com/cr/mo/fullcit?p9904872.
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Kim-Han, Jeong Sook. "Protective role of glutathione peroxidase against levodopa-induced cytotoxicity in PC12 cells." free to MU campus, to others for purchase, 1998. http://wwwlib.umi.com/cr/mo/fullcit?p9904852.
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Borchert, Astrid. "Kodierungsvielfalt der Phospholipid-Hydroperoxid-Glutathion -Peroxidase Untersuchungen zur Expressionsregulation des Enzyms in tierischen Geweben /." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=96896530X.
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Rocha, Anna Silvia Penteado Setti da. "Efeito do selenito de sodio na reparação ossea em tibias de ratos irradiados." [s.n.], 2005. http://repositorio.unicamp.br/jspui/handle/REPOSIP/290156.
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Orientador: Solange Maria de AlmeidaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Sendo a radiação ionizante causador de efeitos deletérios no processo de reparação tecidual e o selenito de sódio um agente antioxidante, atuando contra os radicais livres no organismo, a realização deste trabalho de pesquisa teve como objetivo avaliar o efeito radioprotetor do selenito de sódio no processo de reparação óssea em tíbias de ratos fêmea (Rattus Norvergicus, Albinus, Wistar). A amostra, constituída por 100 ratos, foi dividida em quatro grupos experimentais: controle, irradiado, selênio e selênio/irradiado. Todos os animais foram submetidos a um ato cirúrgico que teve como finalidade a produção de um defeito ósseo nas tíbias direita e esquerda. Os animais dos grupos selênio e selênio/irradiado receberam dose única, via intraperitoneal, de 1 mg/Kg de peso corpóreo de selenito de sódio, sendo que nos animais do grupo selênio/irradiado, a dose foi injetada 15 horas antes destes serem irradiados. A irradiação para os grupos irradiado e selêniolirradiado foi realizada por um aparelho de Cobalto terapia (C06o) com dose simples de 8 Gy nos membros inferiores, após três dias do procedimento cirúrgico. Transcorridos 7, 14, 21, 28 e 45 dias, o processo de reparação óssea foi avaliado em cortes histológicos corados com Hematoxilina Eosina e Tricrômico de Mallory; pela análise ultra-estrutural por microscopia eletrônica de varredura; e quantitativa mente pela densidade volumétrica. Morfologicamente, observou-se que o grupo selênio/irradiado aos 7 dias apresentava-se mais atrasado que o grupo controle, entretanto aos 28 dias os Efeito do Selenito de Sódio na Reparação Óssea em Tíbias de Ratos Irradiados grupos controle, selênio e selênio/irradiado apresentavam um padrão de reparação óssea semelhante, o que também foi observado pela microscopia eletrônica de varredura, aos 45 dias. Quantitativamente, foi observada diferença estatisticamente significante entre as médias de densidade volumétrica para os grupos selênio e selênio/irradiado aos 7, 14 e 28 dias e entre os grupos controle e selênio aos 14 dias. Assim, concluiu-se que o selenito de sódio, apesar de ter-se mostrado tóxico aos sete dias do processo de reparação tecidual, agiu como um eficaz radioprotetor na reparação óssea de tíbias de ratos
Abstract: Considering that the ionizing radiation may cause deleterious effects on the process of tissue repair and sodium selenite is an antioxidant agent, acting against the free radicals in the organism, this study aimed at evaluating the radioprotective effect of sodium selenite on the process of bone repair in tibiae of Wistar rats. The sample comprised 100 rats and was divided into four experimental groups: control, irradiated, selenium and selenium/irradiated. Ali animals were submitted to a surgical procedure for production of a bane defect in the right and left tibiae. The animals in the selenium and selenium/irradiated groups received a single dose of sodium selenite (1 mg/kg of body weight) via intraperitoneal injection; the animals in the selenium/irradiated group received the injection 15 hours before irradiation. The irradiation for the irradiated and selenium/irradiated groups was applied with a cobalt therapy machine (CO60) with simple dose at 8 Gy on the lower limbs, three days after surgery. After 7, 14, 21, 28 and 45 days, the process of one repair was morphologically evaluated by Hematoxylin Eosin and Mallory Trichrome staining; ultrastructural analysis by scanning electron microscopy; and quantitatively evaluated by the volumetric density. As to morphology, it was observed that the selenium/irradiated group at 7 days presented a Iate repair compared to the control group; however, at 28 days, the control, selenium and selenium/irradiated groups presented a similar pattern of bone repair, which was also revealed by scanning electron microscopy at 45 days. Quantitatively, there was a statistically significant difference between the means of volumetric density for the selenium and seleniumlírradiated groups at 7, 14 and 28 days and between the control and selenium groups at 14 days. Thus, it was concluded that sodium selenite, despite being toxic at the seventh day of tissue repair, was an effective radioprotective agent for bone repair in tibiae of rats
Doutorado
Radiologia Odontologica
Doutor em Radiologia Odontológica
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Qi, Xiang, and 祁翔. "The role of glutathione peroxidase 3 (GPx3) : bridging graft injury and tumor invasiveness." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206452.
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Background and Objective:
Severe inflammation resulted from small-for-size liver graft injury provides favorable environment for tumor growth. The oxidative stress not only accelerates the inflammatory response, but also stimulates the proliferation of cancer cells. Therefore, attenuating oxidative stress after liver surgery may not only ameliorate liver injury, but also suppress tumor growth and metastasis. Glutathione peroxidase 3 (GPx3) is an anti-oxidant which has been reported to be down-regulated in several types of cancer. Here, we aimed to investigate the clinical significance of GPx3 and characterize the role of GPx3 in liver graft injury and hepatocellular carcinoma (HCC). Furthermore, we intended to explore the therapeutic value of GPx3 using hiPSC-MSCs as a delivery vehicle in hepatic ischemia-reperfusion injury and HCC.
Materials and methods:
To investigate the clinical significance of GPx3, the HCC patients underwent liver transplantation (106 recipients) or hepatectomy (113 patients) were recruited to study the correlation of GPx3 with clinical parameters. To explore the mechanism of GPx3 in liver graft injury, simulated IR injury model and rat liver transplantation model were applied. To examine the effect of GPx3 on HCC, rGPx3 administration and forced-expression of GPx3 within HCC cells were performed in vitro and in vivo. To explore the therapeutic value of GPx3, engineered hiPSC-MSCs delivering GPx3 was established and applied in mice hepatic IR injury model and nude mice liver cancer model.
Results:
I. The role of GPx3 in graft injury.
The intra-graft GPx3 expression was significantly down-regulated in small-for-size graft accompanied with severe graft injury in a rat liver transplantation model. Clinically, the lower plasma GPx3 was mainly observed in the recipients with small-for-size liver graft. Furthermore, the lower plasma GPx3 significantly correlated with higher tumor recurrence post-transplantation. The down-regulation of GPx3 was associated with hepatic senescence in small-for-size graft. GPx3 treatment delivered by hiPSC-MSCs could significantly ameliorated hepatic IR injury through inhibition of macrophages activation followed by decreased production of ROS, TNFα and IL-1.
II. The role of GPx3 in HCC.
Down-regulation of GPx3 in liver tumor was observed in half of HCC patients (56/113). It significantly correlated with advanced pTNM stage (P = 0.024), presence of venous infiltration (P =0.043) and high AFP level (P = 0.006). The one year (P = 0.038) and five year (P = 0.019) recurrence rate were significantly higher in the patients with lower GPx3 expression. In functional study, rGPx3 administration and over-expression of GPx3 significantly suppressed proliferation and invasiveness of HCC cells in vitro and in vivo. The tumor suppressive activity of GPx3 was mediated by inhibition of EMT through Erk-NFκB-SIP1 pathway. The GPx3 treatment delivered by hiPSC-MSCs could significantly inhibit proliferation of MHCC97L.
Conclusions:
I. Down-regulation of GPx3 was associated with small-for-size graft injury. Low circulating GPx3 at early phase after transplantation predicted higher tumor recurrence of HCC recipients.
II. Down-regulation of GPx3 indicated poor prognosis of HCC patients. GPx3 suppressed tumor growth and invasiveness by inhibition of EMT through Erk-NFκB-SIP1 pathway.
III. Engineered hiPSC-MSCs delivering GPx3 may possess therapeutic value in liver graft injury and HCC.published_or_final_version
Surgery
Doctoral
Doctor of Philosophy
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Hurst, Rachel. "A study of the role of phospholipid hydroperoxide glutathione peroxidase activity in humans." Thesis, University of East Anglia, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.301996.
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Winter, Julian Peter. "Polymorphisms in the glutathione peroxidase-1 gene and the risk of cardiovascular disease." Thesis, University of Leeds, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.423196.
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Gamble, Simon Charles. "Regulation and function of glutathione peroxidase and related antioxidant enzymes in marine invertebrates." Thesis, University of Surrey, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.308490.
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Hille, Jan M. "Die Trinukleotid-Expansion des Gens für zelluläre Glutathion-Peroxidase bei Patienten mit sporadischer amyotropher Lateralsklerose." [S.l.] : [s.n.], 2003. http://deposit.ddb.de/cgi-bin/dokserv?idn=969465327.
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Wortmann, Markus [Verfasser], and Ulrich [Akademischer Betreuer] Pohl. "Glutathion Peroxidase 4 (Gpx4) : ein Modulator der Tumorangiogenese und Endothelintegrität / Markus Wortmann. Betreuer: Ulrich Pohl." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1079477101/34.
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Selles, Benjamin. "Les glutathion peroxydases et protéine disulfure isomérases de peuplier : potentialités du repliement thiorédoxine pour la catalyse des réactions redox." Thesis, Nancy 1, 2011. http://www.theses.fr/2011NAN10028/document.
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La formation de ponts disulfure constitue une modification post-traductionnelle des protéines importante pour de nombreux processus physiologiques, jouant un rôle particulier dans le repliement, la catalyse et la régulation de leur activité. Ce travail concerne l'étude des relations structure-fonction d'oxydoréductases de peuplier appartenant à deux familles de la superfamille des thiorédoxines, les glutathion peroxydases (Gpxs) et les protéine disulfure isomérases (PDIs).L'étude biochimique fine de la Gpx5 a permis de montrer que cette peroxydase réduit le peroxynitrite, propriété inconnue pour ce type de Gpx et de détailler plusieurs étapes du mécanisme catalytique (formation de l'acide sulfénique, changement structural entre formes réduites et oxydées, régénération par les Trxs). La dimérisation de la Gpx5 n'est pas requise pour son activité mais pourrait jouer un rôle dans la reconnaissance de certains substrats. Enfin, l'inactivation de la cystéine peroxydatique par suroxydation suggère que les Gpxs pourraient également avoir une fonction dans la signalisation en réponse aux peroxydes.Concernant les PDIs, suite à une analyse phylogénétique détaillée amenant à proposer une nouvelle classification en 9 classes chez les organismes photosynthétiques, la caractérisation biochimique de plusieurs isoformes présentant des organisations modulaires distinctes et appartenant à trois classes de PDIs a été entreprise. Aucune activité enzymatique typique n'a été identifiée pour la PDI-A, alors que les PDI-L1a et -M possèdent à la fois une activité oxydase et réductase. Les deux modules a de la PDI-M catalysent des réactions spécifiques, de réduction ou d'oxydationProtein activity and folding can be regulated by post-translational modifications that can impact on their physiological functions. One of these is the formation/reduction of disulfide bridges. The aim of the present work is to study the structure-function relationship of protein members of the thioredoxin superfamily, the protein disulfide isomerases (PDI) and the glutathione peroxidases (Gpx).A precise biochemical study has allowed us to demonstrate that this enzyme is an efficient peroxynitrite scavenger, a new finding for this type of protein and allowed investigating several steps of the Gpx5 catalytic mechanism (i.e. sulfenic acid formation, structural changes between reduce dand oxidized forms, Trx-mediated recycling). We also demonstrate that the dimer form of Gpx5 is not absolutely required for peroxide reduction but probably involved in peroxide specificity. Finally, the capability of the peroxidatic cysteine to be overoxidized brings some new clues in favor of an additional signaling function for Gpx5.Concerning PDIs, a detailed phylogenetic analysis of photosynthetic organisms allowed us to identify 9 classes of PDIs and to propose a new nomenclature that fits all these organisms. The biochemical characterization of isoforms of interest has allowed us to highlight some specificity of PDI-L1a and PDI-M in terms of reduction or oxidation reactions catalyzed. A detailed analysis of PDI-M isoform also indicates that the two Trx modules of this protein show differential oxidation or reduction capacities. We could not detect any activity for PDI-A isoforms, leaving us to wonder whether this enzyme is simply active or possesses highly specific protein partners
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Joulain, Catherine. "Influence des modifications de la composition lipidique des membranes sur les mécanismes régulateurs de la réponse lympho-proliferative." Lyon, INSA, 1994. http://www.theses.fr/1994ISAL0101.
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De nombreuses modification de la menbrane lipidique apparaissent dès les premières minutes de l'activation mitogénique. Plusieurs études ont montré que 1es acides gras peuvent agir sur de nombreuses. étapes de la signalisation cellulaire. Ceci nous a conduit à examiner l'effet de différents acides gras polyinsaturés des séries n-6 et n-3 ainsi que 1'effet d'un acide gras mono hydroxylé (le 12-HETE) apportés in vitro à des cellules mononucléées humaines, sur les paramètres biochimiques précoces de l'activation mitogénique. Nous avons tout d'abord montré que ces différents acides gras s'incorporent efficacement dans les phospholipides des cellules mononucléées humaines, et que cette estérification peu influencer la réponse proliférative de ces cellules induite par la ConA. En absence de stimulation mitogénique, les acides gras stimulent l'activité phosphodiestérase (PDE) basale, et, par contre, 1 diminuent notablement la réponse positive de la PDE à la ConA, les acides gras n-3 étant plus actifs que les n-6. Le 12-HETE montre des effets semblables à ceux des acides gras n-3 sur l'activité PDE Le potentiel redox cellulaire peut affecter directement ou indirectement la réponse immune. Il nous a semble important de déterminer si l'enrichissement des membranes cellulaires en acides gras polyinsaturés ou en 12-HETE peut en retour modifier l'activité glutathion peroxydase qui assure normalement la réduction des hydroperoxydes d'acides gras en dérivés ,mono-hydroxylés. Seuls les acides gras de la série n-3, le 20:5(n-3) et le 22:6(n-3), augmentent significativement 1 'activité glutathion peroxydase basale des cellules mononucléées, le traitement par la ConA atténuant l'augmentation de l'activité GPx. Enfin, nous avons mis en évidence une possible liaison spécifique du 12-HETE à la surface des cellules mononucléées humainesNuoerous modification of membrane lipids occur during the first minutes of mitogenic activation. Several studies have shown that fatty acids can affect different steps of cellular signalling process. This led us to examine the in vitro effect of some n-3 and n-6 polyunsaturated fatty acids (PUFA) as well as the effect of a monohydroxylated fatty acid (12(5)-hydroxyeicosatetraenoic acid = 12(5)-HETE) upon the early biochemical events of the mitogenic activation of human peripheral blood mononuclear cells (PBMC}. We have first shown that the studied FA are efficiently esterified in the PM phospholipids and that this esterification can affect ConA-inducedlymphoproliferative response. In the absence of mitogen stimulation, fatty acids, especially n-3 species and 12-HETE, enhance basal phosphodiesterase (PDE) activity and, on the other hand, reduce the ConA, positive PDE response. Cellular redox potential can modify, directly or not, the immune response. Thus, in a second titre, we have investigated Whether PUFA 3nd 12-HETE might in turn modify glutathione-peroxidase (GSH-Px) activity, which is key enzyme involved in the reduction of fatty acid hydroperoxides. Only the n-3 fatty acids, more specifically the 20:5n-3 and 22: 6n-3, can significantly enhance basal GSH-Px activity of PBMc, this effect being attenuated by ConA treatment. Finally, xe have shown a possible specific binding of 12-HETE on PBMC membrane
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Williams, Karin. "Studies on extracellular superoxide dismutase and glutathione peroxidase in the mammalian male reproductive tract." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.246292.
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Fu, Yangxin. "Knockout of Cellular Glutathione Peroxidase Gene Renders Mice Susceptible to Diquat-Induced Oxidative Stress." Kyoto University, 2001. http://hdl.handle.net/2433/151456.
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Garry, Michael R. "Differential response and susceptibility to oxidative stress in mouse lung fibroblasts heterozygous for phospholipid hydroperoxide glutathione peroxidase (GPx4) /." Thesis, Connect to this title online; UW restricted, 2006. http://hdl.handle.net/1773/8465.
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Qatatsheh, Alaaddin. "Interaction between diet, genetic polymorphisms in glutathione peroxidases and susceptibility to ulcerative colitis." Thesis, University of Newcastle Upon Tyne, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416642.
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Santos, Larissa Bezerra. "Polimorfismo Pro198Leu no gene que codifica para a glutationa peroxidase 1 e sua relação com o estado nutricional relativo ao selênio de uma população adulta residente no município de Fortaleza, Ceará." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/9/9132/tde-10092014-114419/.
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O selênio (Se), mineral traço essencial para o ser humano, exerce sua função no organismo por meio de sua participação nas selenoproteínas, dentre as quais destacam-se as glutationas peroxidase (GPx), importantes no sistema de defesa antioxidante. São conhecidas sete isoformas da GPx, sendo a GPx 1 (citosólica) a mais abundante. Como a atividade dessa enzima encontra-se fortemente correlacionada com a concentração sanguínea de Se, este parâmetro é normalmente utilizado como indicador do balanço metabólico do mineral. A concentração de Se nos alimentos depende do local onde foram cultivados e reflete diretamente o teor do mineral no solo, sendo os alimentos da região Norte e Nordeste mais ricos nesse nutriente quando comparados às demais regiões brasileiras. O consumo inadequado de Se provoca uma diminuição da atividade dessa enzima, o que por sua vez pode afetar a proteção antioxidante. Além disso, estudos vêm mostrando que o polimorfismo Pro198Leu no gene da GPx1 também pode diminuir a atividade da GPx. O presente estudo se propôs a verificar a relação entre esse polimorfismo e o estado nutricional relativo ao selênio de uma população adulta residente no município de Fortaleza/Ceará. A população do estudo foi constituída por 176 indivíduos (79 homens e 97 mulheres), com média de idade de 30,4 ± 8,9 anos. Foram realizadas a avaliação da composição corporal por antropometria e a avaliação do consumo alimentar, por meio de três recordatórios de 24h. Os biomarcadores para avaliação do estado nutricional dos indivíduos quanto ao selênio foram: a concentração de Se plasmático e eritrocitário e a atividade da GPx total no eritrócito. Também foi determinado o polimorfismo Pro198Leu no gene que codifica para a GPx 1 por meio de PCR em Tempo Real. Foram encontradas concentrações médias de 62,6 µg/L para Se plasmático e de 101,5 µg/L para Se eritrocitário, não sendo observada correlação entre os dois. A média de ingestão de selênio foi de 76,88 µg/dia, apresentando correlação positiva com o consumo de energia e proteína. Separando por gênero, encontrou-se que as médias de Se plasmático e de Se ingerido dos homens foram significativamente maiores que as das mulheres (p<0,05). A média da atividade da GPx foi de 38,6 U/g Hb. Para o polimorfismo Pro198Leu no gene que codifica para a GPx 1, foram encontrados 96 (54,5%) indivíduos com genótipo selvagem Pro/Pro, 67 (38,1%) indivíduos Pro/Leu e 13 (7,4%) indivíduos Leu/Leu. A frequência encontrada estava em equilíbrio de Hardy-Weinberg. Não foram encontradas diferenças estatísticas significativas nas concentrações de selênio entre os grupos de acordo com o genótipo, no entanto, para a atividade da GPx, houve diferença entre o grupo Pro/Pro e Pro/Leu (p<0,05). No grupo Pro/Pro, foi encontrada correlação positiva entre a concentração de selênio eritrocitário e a atividade eritrocitária total da GPx (p<0,05). Desta forma, podemos concluir que o estado nutricional da população estudada estava adequado com relação ao selênio e que o polimorfismo Pro198Leu apresentou influência sobre a atividade da GPx, que apresentou-se reduzida nos indivíduos que apresentaram alelo variante em seu genótipo.Selenium (Se) is an essential trace mineral for humans which exerts its function in the body in selenoproteins, among which we highlight the glutathione peroxidase (GPx), important in the antioxidant defense system. There are seven known GPx isoforms and the GPx 1 (cytosolic) is the most abundant. As the activity of this enzyme is strongly correlated with selenium blood concentration this parameter is usually used as an indicator of the mineral metabolic balance. Selenium concentration in food depends on the location where they were grown and directly reflects the soil mineral content. Food in the North and Northeast are richer in selenium when compared to other Brazilian regions. Inadequate consumption of Se causes a decrease in GPx activity, what affects the antioxidant protection. Furthermore, studies have shown that the Pro198Leu polymorphism at GPx1 gene of can also decrease the activity of GPx. Our study aimed to investigate the relationship between this polymorphism and nutritional selenium status in an adult population living in Fortaleza/Ceará/Brazil. The study population consisted of 176 individuals (79 men and 97 women) with a mean age of 30.4 ± 8.9 years. The body composition was assessed by anthropometry and the food intake assessment was done using three 24-hour records. The selenium Se concentration was measured in plasma and erythrocyte and GPx activity was measured in erythrocytes. The Pro198Leu polymorphism at GPx 1 gene was determined by Real Time PCR. We found concentrations of 62.6 µg/L for Se plasma and 101.5 µg/L for erythrocyte. There was no correlation observed between these two markers. The average selenium intake was 76.88 µg/day and it showed positively related to the energy and protein consumption. Separating by gender, men selenium plasma concentration and selenium consumption were significantly higher than for women (p < 0.05). The GPx activity was 38.6 U/g Hb. The Pro198Leu polymorphism at GPx 1 gene frequency were 96 (54.5%) subjects with Pro/Pro, 67 (38.1%) subjects Pro/Leu and 13 (7.4%) individuals Leu/Leu. The rate found was in Hardy -Weinberg equilibrium. There were no statistically significant differences in selenium concentrations between groups according to the genotype. However, for GPx activity we found difference between the group Pro/Pro and Pro/Leu (p< 0.05). We also found positive correlation between Se erythrocyte concentration and GPx activity in Pro/Pro group (p<0.05). Thus, we conclude that the selenium nutritional status of the population studied was adequate and that Pro198Leu polymorphism showed influence on the activity of GPx, which was lower in individuals with the variant allele in their genotype.
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Soares, Margarete de Sá. "Avaliação nutricional relativa ao selênio de indivíduos adultos da cidade de Manaus-Amazonas." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/89/89131/tde-04072018-163514/.
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O selênio (Se) é um mineral essencial para o corpo humano, com ação no sistema imunológico, na glândula tireoide, dentre outras funções. É um nutriente importante na proteção das células contra os efeitos dos radicais livres, já que faz parte da enzima glutationa peroxidase (GPX). O consumo alimentar de Se é dependente da concentração desse elemento nos alimentos que varia em função da concentração do mesmo nos solos. Deste modo, este estudo teve como objetivo geral avaliar o estado nutricional relativo ao selênio de indivíduos adultos da cidade de Manaus-AM, por ser considerada região com solo rico nesse nutriente. Casuística: o estudo foi do tipo transversal baseado em amostra não probabilística de conveniência. A população estudada foi composta por 124 voluntários de ambos os gêneros com idade entre 20 a 59 anos. Critérios de inclusão: não ser atleta de elite, não ser etilista, não apresentar doenças crônicas não transmissíveis e não fazer o uso de suplementos vitamínico-minerais e/ou anti-inflamatórios. Não foram incluídos no estudo os participantes que não entregaram os formulários e questionários solicitados (alimentação e/ou ficha cadastral) e/ou que não compareceram para coleta de sangue. A coleta de sangue foi em jejum de 8 a 12 horas para determinação de selênio no plasma e eritrócitos e da atividade da GPX nos eritrócitos, também foram avaliados o consumo alimentar e as medidas antropométricas. Os resultados antropométricos mostraram que 60,0% dos participantes apresentava excesso de peso, a distribuição dos macronutrientes ficou dentro do recomendado pelas DRIs (Dietary Reference Intakes), a ingestão média de selênio ficou acima do recomendado (72±48,0µg/dia), a concentração média para o selênio plasmático foi de 111,4± 37,0 µg/L, de selênio eritrocitário 211± 62,4 µg/L e a atividade da GPX foi de 73± 21,9 U/g Hb, não sendo observada correlação entre as concentrações obtidas para plasma e eritrócito, porém com correlação positiva para Se eritrocitário e atividade da GPX (r= 0,393). Pode-se, portanto concluir do presente estudo que a boa parte dos indivíduos avaliados, habitantes da cidade de Manaus, foi considerada deficiente, apesar de consumirem quantidade desse mineral consideradas adequadas porém, nenhum apresentando parâmetros bioquímicos de deficiência, a maioria dentro da normalidade, entretanto, com um percentual de indivíduos apresentando risco de toxicidade.Selenium (Se) is an essential mineral for the human body, with function on the immune system, thyroid glands and other ones. It is an important nutrient in protecting cells against the effects of free radicals because it is part of glutathione peroxidase enzyme (GPX). Selenium intake depends on the mineral concentration in aliments which varies based on the mineral content in soils. Thus, this study had as main objective to evaluate the nutritional status related to selenium on adults in Manaus-AM because it is considered as a region of high selenium soil content region. Casuistic: This study was transversal type based in a non-probabilistic convenience sample. The population consisted of 124 volunteers (both genders) aged from 20 to 59 years. Inclusion criteria: To not be an elite athlete or alcoholic, do not have chronic non-communicable diseases and do not use vitamin-mineral supplements and/or anti-inflammatory pills. People who did not submit the requested forms and questionnaires (registration form and/or alimentation) and/or did not attend for blood collection were not included. Blood collection was fasting from 8 to 12 hours for determining selenium in plasma and erythrocytes and the activity of GPX in erythrocytes. Food intake and anthropometric measures were also evaluated. Anthropometric results showed that 60,0% were overweight, macronutrient distribution was within the recommended by DRIs (Dietary Reference Intakes). Average selenium intake was above recommended (72±48,0 µg/day), mean plasmatic selenium concentration was 111,4 ± 37,0 µg/L, for erythrocytes selenium was 211 ± 62,4 µg/L and activity of GPX average was 73 ± 21,9 U/g Hb. No correlation between concentration of Se in plasma and erythrocyte, however, there was positive correlation between GPX activity and Se concentration in erythrocytes (r=0,393). Finally, we conclude that most of the people that were evaluated, citizens of Manaus city, were considered as deficient, although they consumed adequate quantities of this mineral. However, none of them showed biochemical deficiency parameters, most within normality, but with a percentage of them showing toxicity risk.
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Silva, Fabiana Veiga da. "Avaliação da influência do polimorfismo Pro198Leu da Glutationa Peroxidase sobre o estresse oxidativo em população exposta ao chumbo." Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/60/60134/tde-09012009-154840/.
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A enzima glutationa peroxidase (GPx-1) possui um importante papel na detoxificação de espécies reativas de oxigênio. Neste estudo foi verificada a influência do polimorfismo Pro198Leu da GPx-1 nos níveis de malondialdeído (MDA) e proteínas carboniladas de 84 voluntários expostos ambientalmente ao chumbo (28 homens e 56mulheres; idade: 18 a 60 anos). Os genótipos para o polimorfismo Pro198Leu da GPx-1 foram determinados por PCR seguido por digestão com enzima de restrição. Chumbo no plasma (Pb_P) e chumbo no sangue total (Pb_S) foram determinados por espectrometria de massas com plasma indutivamente acoplado e espectrometria de absorção atômica com forno de grafite, respectivamente. As freqüências alélicas para os alelos T (que codifica o aminoácido prolina) e C (que codifica o aminoácido leucina) da GPx-1 foram 0,73 e 0,27, respectivamente. Os voluntários foram separados em dois grupos, de acordo com a presença ou ausência do alelo que codifica leucina. Não foi encontrada diferença significativa para as concentrações de Pb_P e Pb_S, bem como para os marcadores de estresse oxidativo entre os grupos. Deste modo, os resultados obtidos sugerem que o polimorfismo Pro198Leu da GPx-1 não torna indivíduos ambientalmente expostos ao chumbo, mais suscetíveis aos danos do estresse oxidativo induzidos pelo metal.Glutathione peroxidase (GPx-1) plays an important role in scavenger reactive oxygen species (ROS). This study was carried out to assess the effects of GPx-1 gene polymorphism (Pro198Leu) on malondialdehyde (MDA) and carbonyl protein ratio in 84 subjects environmentally exposed to lead. Genotypes for the GPx-1 Pro198Leu polymorphism were determined by PCR and restriction fragment length digestion. Lead in plasma (Pb_P) and lead in total blood (Pb_B) were determined by inductively coupled plasma mass spectrometry and by graphite furnace atomic absorption spectrometry, respectively. The allele frequencies for T (which express the proline aminoacid) and C (which express the leucine aminoacid) were 0.73 e 0.27, respectively. The volunteers were divided in two groups, according to the presence or absence of C allele. No significant differences were found in Pb_P and Pb_B, as well as for the other oxidative biomarkers between the groups. Therefore, the obtained results suggest that the GPx-1 Pro198Leu polymorphism do not affect individuals environmentally exposed to lead greater susceptible to oxidative damage induced for this metal.
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Sudati, Jessie Haigert. "Toxicologia e farmacologia in vitro de novos compostos orgânicos de selênio e telúrio com atividade tipo tiol peroxidase." Universidade Federal de Santa Maria, 2009. http://repositorio.ufsm.br/handle/1/11104.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoGlutathione peroxidase (GPx; EC 1.11.1.9) is a well-known selenoenzyme that catalyzes the reduction of hydrogen peroxide and some organic hydroperoxides by glutathione (GSH) and protects lipid membranes and other cellular components against oxidative stress, which is related to many diseases and this enzyme is regarded as one of the most important antioxidant enzymes in living organisms. Because the natural GPx has some shortcomings (e.g. instability and poor availability), scientists have paid more attention to its artificial imitation. Synthetic organoselenium and organotellurium compounds have emerged as excellent candidates to act as GPx mimics. Thus, in this study, several aminoacids derivatives containing selenium or tellurium were tested in order to evaluate their in vitro (i) GPx mimic properties (or GPx like activity) according to the model reaction (H202 + 2PhSH → PhSSPh + 2H20); (ii) catalytic properties, (iii) reactivity with low molecular weight thiols (reduced glutathione, captopril and dithiothreitol) and (iv) their effect against lipid peroxidation have been performed. All compounds tested in this study showed ability to imitate de antioxidant enzyme GPx, but this property showed a dependence on the aminoacid residue and steric effect. Compounds C, D and 7g derivatives were found as the best catalysts in reducing peroxides, in comparison with other compounds tested. These results suggest that aminoacids derivatives compounds containing selenium or tellurium used in this work can be considered promising GPx mimetics.
A Glutationa Peroxidase (GPx; EC 1.11.1.9) é uma selenoenzima que catalisa a redução do peróxido de hidrogênio e hidroperóxidos orgânicos na presença de glutationa (GSH). Sua ação catalítica evita, desta forma, a oxidação dos lipídios constituintes da membrana, bem como de outros componentes celulares. Sabe-se que a produção excessiva de espécies reativas de oxigênio (EROs) está relacionada ao surgimento de muitas doenças, e a enzima GPx é considerada uma das mais importantes enzimas antioxidantes presentes nos organismos vivos, sendo necessária para auxiliar na proteção contra estas patologias. No entanto, a enzima GPx possui algumas desvantagens tais como, instabilidade e pouca viabilidade no que diz respeito a uma possível administração oral ou endovenosa, por isso, surgiu o interesse na síntese de compostos que possam mimetizar o mecanismo de ação dessa enzima. Dados da literatura têm demonstrado que os compostos orgânicos sintéticos de selênio (Se) e telúrio (Te) são excelentes miméticos da enzima GPx. Assim, neste estudo, uma série de compostos orgânicos derivados de aminoácidos contendo Se e Te na estrutura foram testados com a finalidade de avaliação in vitro da (i) atividade mimética da GPx (ou tipo GPx, isto é, GPx like activity ) de acordo com a reação H2O2 + 2PhSH PhSSPh + 2H2O; (ii) propriedades catalíticas destes compostos, (iii) reatividade e possível oxidação dos compostos tiólicos de baixo peso molecular (glutationa reduzida, captopril e ditiotreitol) e o (iv) efeito contra a peroxidação lipídica. Todos os compostos utilizados neste trabalho demonstraram atividade mimética à GPx; porém, essa propriedade apresentou uma dependência em relação ao resíduo de aminoácido presente na estrutura do composto, bem como influência estérica. Os disselenetos C, D e os derivados do telureto 7g foram os mais eficazes na redução de peróxidos quando comparados aos demais compostos utilizados neste estudo. Portanto, estes resultados sugerem que os compostos orgânicos derivados de aminoácidos contendo Se ou Te podem ser considerados miméticos importantes da GPx.
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Canata, Diego Mena. "Perfil redox da classificação clínica de polipose nasal." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/143816.
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Introdução: A polipose nasal (PN) é considerada uma condição inflamatória crônica da mucosa da cavidade nasal e seios paranasais de etiologia não muito clara. Há poucos dados sobre alterações epiteliais em PN e sua relação com a ação dos radicais livres. Muitas doenças estão ligadas a danos causados por espécies reativas de oxigênio (ROS) e de nitrogênio (RNSS) e ocorrem de um desequilíbrio entre eles e antioxidantes, o que for maior atividade de espécies reativas, o que chamamos de estresse oxidativo. Objetivo: O objetivo principal deste estudo é avaliar o estresse oxidativo em pólipos removidos cirurgicamente em 3 grupos de pacientes com polipose nasal (com PN unicamente, PN associado à asma e PN associado à asma e intolerância ao ácido acetilsalicílico) a fim de elucidar possíveis diferenças no perfil redox nestes grupos. Material e Métodos: Cinquenta e nove pacientes com diagnóstico de polipose nasal foram divididos em três grupos clínicos: um grupo controle PN unicamente, um grupo asma (PN associado à asma) e um grupo Widal (PN associado à asma e intolerância ao ácido acetilsalicílico). Medição e Resultados Principais: Neste trabalho defesas enzimáticas (superóxido dismutase, consumo de peróxido de hidrogênio, glutationa peroxidase e glutationa S-transferase) e defesas não enzimáticas (glutationa total, nitritos e nitratos, vitamina C e E) foram analisados. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo asma, o consumo de peróxido de hidrogênio, atividade da glutationa peroxidase, níveis de malondialdeído e vitamina E foram significativamente menores do que no grupo de controle. Também foi realizada a medição de danos em lipídios (malondialdeído) e proteínas (carbonila). No grupo Widal foram encontrados níveis significativamente maiores de glutationa e nitritos e nitratos em relação ao grupo controle. Não foram encontradas diferenças entre os grupos em relação ao nível de carbonila e glutationa, tamanho dos pólipos, atividades da superóxido dismutase e S-transferase. Conclusões: A classificação redox dos grupos de PN foi parcialmente alcançada. Os pólipos do grupo asma possuem alterações nas defesas enzimáticas relacionadas com o peróxido de hidrogênio e a peroxidação lipídica, enquanto pólipos do grupo Widal apresentaram alterações nos níveis de óxido nítrico e glutationa.Introduction: Nasal polyposis (NP) is considered a chronic inflammatory condition of the mucosa of the nasal cavity and paranasal sinuses of etiology is not very clear. There are few data on epithelial changes in nasal polyposis and its relation to the action of free radicals. Many diseases are linked to damage caused by reactive oxygen species (ROS) and nitrogen (RNSs) and occur from an imbalance between them and antioxidants, whichever is greater activity of reactive species, what we call oxidative stress. Objective: The primary objective of this study is to evaluate oxidative stress in polyps surgically removed in 3 groups of patients with nasal polyposis, in order to elucidate possible differences in redox profile in these groups. Methods: Fifty nine patients diagnosed with nasal polyposis were divided into three groups: a control group, an asthma group (NP with asthma) and a Widal group (NP with asthma and aspirin intolerance) in which patients had an association of NP, asthma and aspirin intolerance. Measurement and main results: In this work enzymatic defenses (superoxide dismutase, hydrogen peroxide consumption, glutathione peroxidase and glutathione S-transferase) and non-enzymatic defenses (total glutathione, measurement of nitrites and nitrates, vitamin C and E) were analyzed. Also the measurement of damage in lipids (malondialdehyde) and proteins (carbonyl) was conducted. In the asthma group, hydrogen peroxide consumption, glutathione peroxidase activity, malondialdehyde, and vitamin E levels were significantly lower than in the control group. The Widal group showed significant higher glutathione levels, nitrite and nitrate levels than found in the control group. No differences were found among the groups regarding carbonyl level, polyp size, superoxide dismutase, and glutathione S-transferase activities. Conclusions: The redox classification of the groups of NP was partly achieved. Polyps of patients with asthma have changes in enzymatic defense pathways related to hydrogen peroxide and lipid peroxidation while polyps of patients with Widal triad present changes in nitric oxide and glutathione.
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ANTEBI-MACHALOVA, HELENA. "Effet de l'ethanol sur le metabolisme hepatique et cerebral du glutathion chez le rat : action de la desferrioxamine b." Paris 6, 1986. http://www.theses.fr/1986PA066525.
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L'administration de desferrioxamine (chelateur du fer et capteur du radical superoxyde) a des animaux soumis a une intoxication alcoolique aigue ou chronique previent la baisse de la teneur en glutathion dans les tissus hepatiques et cerebraux. L'elevation de l'activite de la glutathion peroxydase et de la glutathion reductase representerait un mecanisme d'adaptation aux concentrations elevees de lipoperoxydes observees lors de l'intoxication alcoolique chronique
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Collins, Catriona Ann. "Redox-catalysts with glutathione peroxidase and metallothionein antioxidant activity that counteract oxidative stress in rheumatoid arthritis." Thesis, University of Exeter, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.437465.
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Chada, Sunil. "A Molecular Analysis of Selenium Incorporation into Glutathione Peroxidase: Stop Is Not the End: A Thesis." eScholarship@UMMS, 1989. http://escholarship.umassmed.edu/gsbs_diss/154.
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Selenium is toxic at high doses, yet metabolically essential in trace amounts, and therefore provides an excellent illustration of the rule of paracelsus that "the dose alone determines the poison". The only mammalian selenoprotein of known function is glutathione peroxidase (GPx). This enzyme is expressed ubiquitously, and is responsible for detoxifying peroxides and hydroperoxides which, if left unchecked, may damage important biomolecules such as DNA and membrane fatty-acids. GPx is a homotetramer; each subunit contains one mole atom of selenium incorporated as a selenocysteine residue in the active site of the enzyme.
Using oligonucleotides generated against the known bovine GPx amino-acid sequence, cDNA clones were isolated corresponding to the human GPx mRNA. Sequence analysis indicated that the selenocysteine in the active site of the enzyme was incorporated at an opal terminator (UGA) codon. Therefore the glutathione peroxidase mRNA constitutes the first example of natural suppression of a terminator codon in human cells.
Regulation of human GPx gene expression by selenium was examined. Selenium replete HL-60 cells possessed approximately 30-fold more enzymatic GPx activity than selenium deficient cells. However steady-state GPx mRNA levels and rate of transcription of the GPx gene differed by less than 1.5-fold. Cycloheximide abolished the increase in enzymatic activity observed upon selenium replenishment. Cellular immunoreactive GPx protein levels correlated with enzymatic activity, indicating that the human GPx gene is regulated post-transcriptionally by selenium. The mechanism of this post-transcriptional regulation was investigated.
A selenium labelled tRNA species was identified which exhibited features in common with a previously characterized tRNAUGA. This data suggested that selenium may be incorporated into GPx via a co-translational mechanism using a selenocysteinyl tRNA intermediate. Selenium did not alter cytoplasmic levels of the tRNAUGA, indicating that accumulation of cytoplasmic suppressor tRNA was not the point of regulation of GPx by selenium. A model is proposed for the co-translational insertion of selenocysteine into GPx mediated by a charged tRNA species present in selenium replete but absent from selenium deficient cells. Models are also proposed to explain the discrimination between the selenocysteine UGA codon and authentic UGA terminator codons.
The regulation of the GPx gene was examined during mono-myelocytic differentiation of HL-60 cells in vitro and also during interferon-gamma activation of human peripheral blood macrophages and PMN. During phagocyte cell differentiation or activation, the ability to generate peroxide developed, however the peroxide-destroying capacities of GPx did not increase concomitantly. Complex regulatory patterns involving both transcriptional and translational controls were observed.
The association of GPx gene expression with chronic granulomatous disease was explored. No correlation was found with either the autosomal or X-linked forms of the disease, a finding contradictory to previously published material.
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Patel, Shreenal Harishchandra. "Structural insight into the catalytic mechanism of the unique glutathione-dependent peroxidase enzymes of Trypanosoma cruzi." Thesis, University College London (University of London), 2007. http://discovery.ucl.ac.uk/1446276/.
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Kinetoplastid parasites cause a variety of diseases including African sleeping sickness (Trypanosoma brucei) and Chagas disease (Trypanosoma cruzi). The invading parasite is exposed to reactive oxygen species (ROS) generated from the host immune response. In trypanosomes, the glutathione/glutathione reductase antioxidant system (present in the host), is replaced by the analogous trypanosome-specific trypanothione/trypanothione reductase antioxidant system. The differences in the unique oxidative defence system of the parasite from its host, provides potential drug targets. The parasites, like their mammalian hosts, possess glutathione-dependent peroxidase enzymes (GPX), which have a conserved active site cysteine (analogous to selenocysteine in the mammalian hosts). Research now considers these enzymes to fall into a mechanistic family similar to peroxiredoxin enzymes. Peroxiredoxins are a large family of proteins, whereby members fall into the subgroups according to the number of active site cysteine residues present and their distribution (1-Cys or 2Cys typical/atypical). It was recently found that T. brucei glutathione peroxidase enzyme (TbPxIII) follows a mechanism analogous to atypical 2-Cys peroxiredoxin mechanism, supporting a similar mechanism in the homologue T. cruzi glutathione peroxidase I (TcGPXI). The aim of my thesis work was to gain structural information on TcGPXI, to provide insight into the mechanism of this enzyme. Constructs of TcGPXI, TcGPXII, TbPxI and TbPxII were cloned, expressed and purified to produce sufficient protein for structural studies. TcGPXI was investigated by NMR spectroscopy, which facilitated 96% backbone sequence assignments and secondary structure prediction for oxidised wild type TcGPXI. An intra-molecular disulphide bond was observed between the conserved catalytic cysteine and a second cysteine within the protein sequence. To investigate this, cysteine mutants were created to break the disulphide bond and investigated with NMR techniques. Additionally, sequence-specific backbone assignments were obtained for reduced wild type TcGPXI. Established kinetic assays were used to assess catalytic activity. The mutant enzymes exhibited no activity, suggesting that both cysteines involved in the intramolecular disulphide bond, are required for catalysis. Protein from constructs of TcGPXII. TbPxI, TbPxII and oxidised wild type TcGPXI (including mutant forms) were subjected to crystallisation screens. Diffraction data for oxidised wild type TcGPXI was collected, at a resolution of 2.3 A. Molecular replacement was used to solve the crystal structure of TcGPXI. The work presented in this thesis will show that TcGPXI follows a new mechanistic family of enzymes, similar to that of the atypical 2-Cys peroxiredoxin family. The crystal structure reveals the possibility of a disulphide bond in the oxidized state, associated with the unravelling of a helix otherwise present in the thioredoxin fold.
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Grünler, Nadine [Verfasser], and Ulrich [Akademischer Betreuer] Hoffmann. "Untersuchungen zur Rolle der Glutathion-Peroxidase 4 als möglicher Redox-Sensor in Säugetierzellen / Nadine Grünler. Betreuer: Ulrich Hoffmann." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2015. http://d-nb.info/1072376504/34.
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Hadley, Kevin B. "Differential regulation of selenoenzymes by SE status in mammals and birds /." free to MU campus, to others for purchase, 2001. http://wwwlib.umi.com/cr/mo/fullcit?p3025622.
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Aksamit, Matthew Stephen. "Bioinformatic analysis of pea aphid salivary gland transcripts." Thesis, Kansas State University, 2014. http://hdl.handle.net/2097/32836.
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Master of ScienceBiochemistry and Molecular Biophysics Interdepartmental Program
Gerald Reeck
Pea aphids (Acyrthosiphon pisum) are sap-sucking insects that feed on the phloem sap of some plants of the family Fabaceae (legumes). Aphids feed on host plants by inserting their stylets between plant cells to feed from phloem sap in sieve elements. Their feeding is of major agronomical importance, as aphids cause hundreds of millions of dollars in crop damage worldwide, annually. Salivary gland transcripts from plant-fed and diet-fed pea aphids were studied by RNASeq to analyze their expression. Most transcripts had higher expression in plant-fed pea aphids, likely due to the need for saliva protein in the aphid/plant interaction. Numerous salivary gland transcripts and saliva proteins have been identified in aphids, including a glutathione peroxidase. Glutathione peroxidases are a group of enzymes with the purpose of protecting organisms from oxidative damage. Here, I present a bioinformatic analysis of pea aphid expressed sequence tag libraries that identified four unique glutathione peroxidases in pea aphids. One glutathione peroxidase, ApGPx1 has high expression in the pea aphid salivary gland. Two glutathione peroxidase genes are present in the current annotation of the pea aphid genome. My work indicates that the two genes need to be revised.
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Nxele, Xolisa. "A biochemical and proteomic analysis of sugargraze sorghum under hyperosmotic stress." University of the Western Cape, 2015. http://hdl.handle.net/11394/4308.
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>Magister Scientiae - MScSugargraze is a moderately drought tolerant sweet sorghum hybrid which is ideal for grazing, winter stand over and pit silage. A major advantage that Sugargraze has over other forages is its very high sugar content which improves feed quality thus increasing palatability and results in significantly reduced feed wastage. This study explored the influence of hyperosmotic stress on plant development, ROS accumulation, antioxidant capacity and the extent of cell death. Heat shock protein (Hsp70) expression immunoblotting assays were used to demonstrate whether the various treatment conditions induced stress within natural physiological parameters for the experimental material. This was coupled with the separation, visualization and identification of abundant proteins in Sugargraze leaves in response to hyperosmotic stress using two-dimensional gel electrophoresis (2-DE) in combination with mass spectrometry (MS). The results showed that hyperosmotic stress significantly influences plant development by reducing plant biomass and increasing the levels of ROS accumulation, proline content and subsequently reducing total chlorophyll content. An over accumulation of ROS in the form of hydrogen peroxide and lipid peroxidation was observed in the stressed plants which was supported by the extent of cell death. Although an increase in antioxidant enzyme activity (in the form of total enzymatic activity or individual isoform activity) in response to hyperosmotic stress was observed, this increase was not sufficient to counter the deleterious effects caused by the stress conditions hence the decrease in plant biomass and increase in cell death. Western blotting analysis of Sugargraze leaf tissues using Hsp70 antibodies showed that hyperosmotic stress induced Hsp70 expression to levels significantly higher than observed for the control plants. A total of thirteen CBB stained spots were selected for mass spectrometric identification, owing to their good resolution and abundance levels, and of these, nine were positively identified. Identified proteins were divided into functional categories including both known and novel/putative stress responsive proteins. Molecular and physiological functions of some of the proteins of interest identified will be subjected to further investigation via bioinformatic and molecular biology approaches.
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Mannes, Alexander Markward. "Dissecting the role of selenothiol- versus thiol-based catalysis using the model enzyme glutathione peroxidase 4 (GPx4)." Diss., Ludwig-Maximilians-Universität München, 2014. http://nbn-resolving.de/urn:nbn:de:bvb:19-170110.
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Selenocysteine (Sec) is the 21st amino acid. Unlike other amino acids incorporation of Sec into proteins is more complex by far as it is encoded by the opal stop codon UGA. A complex and highly sophisticated incorporation mechanism is required in order to assure the correct co-translational incorporation of Sec into the nascent polypeptide chain. Even after years of intensive research the question as to why selenoproteins are important for mammalian life has not been fully understood. This study aimed to provide answers to this question using gluthathione peroxidase 4 (GPx4) as a model enzyme. It has been shown that GPx4 is essential for early embryogenesis, neuro- and retina-protection and male fertility in mice. But the role of selenothiol- versus thiol-based GPx4 catalysis in cells and mice, as well as the role of the catalytic tetrad in GPx4 catalysis and the subcellular localisation of the different GPx4 isoforms and their impact on cell protection have remained unclear. Therefore, a series of mutant variants of GPx4 were generated by site-directed mutagenesis, stably expressed in tamoxifen-inducible GPx4 knockout cells (Seiler et al., Cell Metab 2008), and functionally analysed. GPx4 mutant variants included those of the peroxidatic Sec, the catalytic tetrad, the mitochondrial leader sequence (Mls) and the non-peroxidatic cysteines. These studies revealed that Cys can functionally replace Sec in the active centre of GPx4 to a large extent in cells, whereas some amino acids of the catalytic site are necessary for GPx4 function. None of the non-peroxidatic Cys were shown to be required for the cell-protective function of GPx4, ruling out a possible resolving Cys in the catalytic cycle of GPx4 unlike homologues in other organisms that use a resolving Cys. The fuction of a resolving Cys is to start a nucleophilic attack upon the intermolecular bond between the peroxidatic Cys and the substrate in order to create an intramolecular disulfidbride. Apparently subcellular localization of GPx4 in the extramitochondrial/cytosolic compartment is crucial for its cell death preventing qualities as overexpression of mitochondrial GPx4 in the knockout cells failed to rescue cell death induced by endogenous GPx4 disruption.Bei Selenocystein (Sec) handelt es sich um die 21igste Aminosäure. Im Gegensatz zu anderen Aminosäuren ist der Einbau von Selenocystein in die entstehende Polypeptidkette sehr viel komplexer, da Sec von dem Opal Stopcodon UGA codiert wird. Eine komplexe und hochentwickelte Maschinerie ist erforderlich um den korrekten, ko-translationalen Einbau von Sec in Proteine zu gewährleisten. Auch nach Jahren intensiver Forschung ist es immer noch weitgehend unklar, warum Selenoproteine für das Säugerleben unverzichtbar sind. Diese Studie hatte deshalb zum Ziel, diese Frage etwas genauer zu beleuchten, wobei die Glutathion-Peroxidase 4 (GPx4) als Modellenzym verwendet wurde. Es ist bekannt, dass GPx4 sowohl für die Embryonalentwicklung, den Schutz von Neuronen und der Retina sowie für die männliche Fertilität von Mäusen unverzichtbar ist. Dennoch sind viele Fragen bezüglich der Funktionsweise und möglicher Unterschiede von Selenothiol- zu Thiolbasierter GPx4 Katalyse in Zellen und Mäusen ungeklärt. Ebenso wie die genaue Funktion der katalytischen Tetrade bei der GPx4 Katalyse, und die subzellulare Lokalisation der verschiedenen GPx4 Isoformen und deren Einfluß auf den zellulären Schutz bislang ungeklärt sind. Deswegen wurden in dieser Arbeit eine Reihe von GPx4 Mutanten durch zielgerichtete Mutagenese erzeugt. Diese wurden stabil in Tamoxifen-induzierbaren GPx4 knockout Zellen (Seiler et al., Cell Metab 2008) exprimiert und auf ihre Funktionalität analysiert. Die verschiedenen GPx4 Mutationen beinhalteten Mutanten des Sec im aktiven Zentrum, der katalytischen Tetrade, der mitochondrialen Signalsequenz (Mls) sowie der nicht peroxidativen Cysteine. Die hier vorgelegten Untersuchungen zeigen, dass Cys in der Lage ist das Sec im aktiven Zentrum, unter Aufrechterhaltung eines Großteils der Funktionalität, in der Zelle zu ersetzen, wohingegen einige der Aminosäuren der katalytischen Tetrade unentbehrlich für die Funktionalität von GPx4 sind. Keines der übrigen, in GPx4 vorhandenen, Cys wurde benötigt, um die zelluläre Schutzwirkung von GPx4 aufrecht zu erhalten. Dieses Ergebnis schließt die Existenz eines auflösenden Cys im katalytischen Kreislauf von GPx4 aus. Dies steht im Gegensatz zu den Cys tragenden Homologen in anderen Organismen, welche über ein auflösendes Cys verfügen. Die Funktion des auflösenden Cys besteht darin, einen nukleophilen Angriff auf die intermolekulare Bindung zwischen dem peroxidativen Cys und dem Substrat zu starten. Durch diesen Angriff wird die intermolekulare Bindung in eine intramulekulare Disulfidbrücke umgewandelt. Die Lokalisation von GPx4 im extramitochondrialen/cytosolischen Raum ist zudem entscheidend für den Schutz vor Zelltod, da eine Überexpression der mitochondrialen GPx4 nicht in der Lage war, den durch Ausschalten der endogenen GPx4 verursachten Zelltod zu verhindern.
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Ali, Johar. "Performance, tissue selenium concentration and glutathione peroxidase activity as response variables for determining selenium requirements of poultry /." free to MU campus, to others for purchase, 2000. http://wwwlib.umi.com/cr/mo/fullcit?p9999267.
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Lewin, Michelle Helen. "Thioredoxin reductase and glutathione peroxidase in the prevention of oxidative damage to vascular endothelium and the skin." Thesis, University of Edinburgh, 2004. http://hdl.handle.net/1842/24829.
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Brault, Charlène. "Modulation du stress oxydant par le virus de l'hépatite C et identification de propriétés pro virales de l'antioxydant GPx4." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10095.
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L’infection par le virus de l’hépatite C (VHC) évolue généralement vers le développement d’une hépatite C chronique, fréquemment associée à des perturbations métaboliques, (insulinorésistance et stéatose), et de la structure hépatique (fibrose et cirrhose), favorisant le développement d’un hépatocarcinome. Le stress oxydant semble étroitement lié à la progression de ces pathologies, notamment l’insulino-résistance. Or, les mécanismes moléculaires par lesquels le VHC module le stress oxydant restent confus, ainsi que l’effet réciproque du stress oxydant sur la réplication virale. Jusqu’à récemment, la modulation de ce stress a été étudiée in vitro dans des modèles non réplicatifs du VHC ou dans des modèles d’expression ectopiques des protéines virales. Peu d’études ont encore tenté de caractériser l’effet d’une infection complète et productive dans les cellules cibles naturelles du VHC, les hépatocytes. Mes travaux de recherche ont donc consisté à étudier la modulation de la balance redox cellulaire dans un modèle d’infection complet de type HCVcc, et dans les cellules hépatocytaires Huh7.5. Cette étude a permis de caractériser le stress oxydant dans ce modèle, mais surtout d’identifier un antioxydant à activité pro-virale, la glutathion peroxydase 4 (GPx4). En effet, nous avons observé une stimulation viro-induite de l’expression et de l’activité de GPx4, seule enzyme capable de détoxifier les lipides membranaires oxydés. L’expression de cette enzyme semble nécessaire à la réplication ainsi qu’à l’infectivité virale. Son importance pour le VHC résiderait dans son activité catalytique permettant de maintenir l’intégrité des lipides cellulaires nécessaire au cycle viralChronic infection with Hepatitis C virus (HCV) is frequently associated with metabolic disturbances (insulin-resistance and steatosis) as well as with changes to hepatic structure (fibrosis and cirrhosis) that favor hepatocellular carcinogenesis. Insulin resistance is in particular linked to oxidative stress, which is thought to play a key role in driving disease progression. However, molecular mechanisms by which HCV regulates oxidative stress are still unclear and reciprocally, the effect of oxidative stress on viral life cycle is not well understood. Until recently, induction of oxidative stress by HCV has mainly been investigated in non replicative in vitro models or in cell systems expressing viral proteins alone. Few studies have yet investigated oxidative stress in the context of productive HCV infection. My work consisted of studying the modulation of the cellular redox system using the HCVcc infection model, based on a replicative HCV isolate and the hepatoma cell line Huh7.5. This work provided a broad characterization of how HCV induces and prevents oxidative stress and identified glutathion peroxidase 4 (GPx4) as a pro-viral antioxydant enzyme. Indeed, we observed an HCVinduced upregulation of expression and activity of GPx4. We also demonstrated that GPx4 expression is required for viral replication and infectivity. As GPx4 possesses a particular catalytic activity, which is the detoxification of oxidized membrane lipids, we investigated the impact of the accumulation of oxidized lipids on HCV replication. These studies showed that GPx4 is an important host factor for HCV life cycle by maintaining membrane lipid integrity in an oxidative cellular environment
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Patrick, Sarah A. "Neuroprotective Effects of Pramlintide Against Oxidative Stress and Alzheimer's Disease." Kent State University / OhioLINK, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=kent1524145067277978.
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Attacha, Safira [Verfasser]. "Subcellular localization of Glutathione peroxidase-like enzymes in Arabidopsis thaliana and characterization of GPXL3 deficient mutants / Safira Attacha." Bonn : Universitäts- und Landesbibliothek Bonn, 2017. http://d-nb.info/1129874109/34.
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Buday, Katalin Judit [Verfasser], Wolfgang [Akademischer Betreuer] Wurst, Wolfgang [Gutachter] Wurst, and Jan [Gutachter] Riemer. "Functional characterization of glutathione peroxidase 8 (GPX8) / Katalin Judit Buday ; Gutachter: Wolfgang Wurst, Jan Riemer ; Betreuer: Wolfgang Wurst." München : Universitätsbibliothek der TU München, 2020. http://d-nb.info/1226934102/34.
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