Дисертації з теми "Thioredoxin; oxidative stress"
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Gregory, Mary Sarah-Jane, and n/a. "Thioredoxin and Oxidative Stress." Griffith University. School of Health Science, 2004. http://www4.gu.edu.au:8080/adt-root/public/adt-QGU20040301.082639.
Повний текст джерелаFindlay, Victoria Jane. "The role of thioredoxin peroxidases in the yeast oxidative stress response." Thesis, University of Newcastle Upon Tyne, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391954.
Повний текст джерелаSusanti, Dwi. "Sulfite reductase and thioredoxin in oxidative stress responses of methanogenic archaea." Diss., Virginia Tech, 2013. http://hdl.handle.net/10919/51423.
Повний текст джерелаOur laboratory is interested in studying the mechanism underlying the oxygen tolerance and oxidative stress responses in methanogenic archaea, which are obligate anaerobe. Our research concerns two aspects of oxidative stress. (i) Responses toward extracellular toxic species such as SO32-, that forms as a result of reactions of O2 with reduced compounds in the environment. These species are mostly seen in anaerobic environments upon O2 exposure due to the abundance of reduced components therein. (ii) Responses toward intracellular toxic species such as superoxide and hydrogen peroxide that are generated upon entry of O2 and subsequent reaction of O2 with reduced component inside the cell. Aerobic microorganisms experience the second problem. Since a large number of microorganisms of Earth are anaerobes and the oxidative defense mechanisms of anaerobes are relatively less studied, the research in our laboratory has focused on this area. My thesis research covers two studies that fall in the above-mentioned two focus areas.
In 2005-2007 our laboratory discovered that certain methanogens use an unusual sulfite reductase, named F420-dependent sulfite reductase (Fsr), for the detoxification of SO32- that is produced outside the cell from a reaction between oxygen and sulfide. This reaction occurred during early oxygenation of Earth and continues to occur in deep-sea hydrothermal vents. Fsr, a flavoprotein, carries out a 6-electron reduction of SO32- to S2-. It is a chimeric protein where N- and C-terminal halves (Fsr-N and Fsr-C) are homologs of F420H2 dehydrogenase and dissimilatory sulfite reductase (Dsr), respectively. We hypothesized that Fsr was developed in a methanogen from pre-existing parts. To begin testing this hypothesis we have carried out bioinformatics analyses of methanogen genomes and found that both Fsr-N homologs and Fsr-C homologs are abundant in methanogens. We called the Fsr-C homolog dissimilatory sulfite reductase-like protein (Dsr-LP). Thus, Fsr was likely assembled from freestanding Fsr-N homologs and Dsr-like proteins (Dsr-LP) in methanogens. During the course of this study, we also identified two new putative F420H2-dependent enzymes, namely F420H2-dependent glutamate synthase and assimilatory sulfite reductase.
Another aspect of my research concerns the reactivation of proteins that are deactivated by the entry of oxygen inside the cell. Here I focused specifically on the role of thioredoxin (Trx) in methanogens. Trx, a small redox regulatory protein, is ubiquitous in all living cells. In bacteria and eukarya, Trx regulates a wide variety of cellular processes including cell divison, biosynthesis and oxidative stress response. Though some Trxs of methanogens have been structurally and biochemically characterized, their physiological roles in these organisms are unknown. Our bioinformatics analysis suggested that Trx is ubiquitous in methanogens and the pattern of its distribution in various phylogenetic classes paralleled the respective evolutionary histories and metabolic versatilities. Using a proteomics approach, we have identified 155 Trx targets in a hyperthermophilic phylogenetically deeply-rooted methanogen, Methanocaldococcus jannaschii. Our analysis of two of these targets employing biochemical assays suggested that Trx is needed for reactivation of oxidatively deactivated enzymes in M. jannaschii. To our knowledge, this is the first report on the role of Trx in an organism from the archaeal domain.
During the course of our work on methanogen Trxs, we investigated the evolutionary histories of different Trx systems that are composed of Trxs and cognate Trx reductases. In collaboration with other laboratories, we conducted bioinformatics analysis for the distribution of one of such systems, ferredoxin-dependent thioredoxin reductase (FTR), in all organisms. We found that FTR was most likely originated in the phylogenetically deeply-rooted microaerophilic bacteria where it regulates CO2 fixation via the reverse citric acid cycle.
Ph. D.
Walther, Ashley Elizabeth. "Role of the Schizosaccharomyces pombe Enzyme Thioredoxin Peroxidase in Oxidative Stress Resistance." Thesis, Boston College, 2006. http://hdl.handle.net/2345/420.
Повний текст джерелаWithin cells, reactive oxygen species (ROS) are synthesized naturally and in response to environmental stimuli. However, ROS have deleterious effects on a wide range of cellular molecules. Oxidative stress, caused by the ROS generated by the partial reduction of oxygen, is a major cause of cell damage linked to the initiation and progression of numerous diseases. Thioredoxin peroxidase (Tpx1) plays important roles in cellular defense against ROS. Although homologous genes and their functions have been identified in other eukaryotes, the level of activity as well as the necessity of this protective enzyme in S. pombe exposed to oxidative stress has yet to be fully elucidated. To explore the role of the Tpx1 protein in oxidative stress resistance, novel strains were constructed in which the tpx1 gene was overexpressed. The polymerase chain reaction was used to amplify txp1, and the amplified sequence was cloned into the yeast overexpression plasmid, pNMT41, which allows overexpression under the control of the powerful promoter. DNA sequencing was used to determine that the sequences had been properly inserted into the vector. The plasmids were transformed into two leu- yeast strains: FWP6 and TP108-3C. Production of the Tpx1 protein was ensured using Western Blot techniques. Experimentation to test the responses of the tpx1 strain to oxidative stress will employ a variety of reactive oxygen generators, including hydrogen n peroxide, menadione, tert-butyl hydroperoxide, and paraquat. The results generally supported the proposed role of Tpx1 to confer additional resistance against the oxidative stress. In a complementary line of investigation, knockout strains are being constructed to reduce the levels of the Tpx1 in S. pombe. Gene deletion cassettes were constructed for tpx1. Currently, the strains are being analyzed for the successful replacement of the endogenous tpx1 gene by homologous recombination. If the absence of the protein results in decreased cell viability, the role of Tpx1 indicated by the overexpression experiments could be supported
Thesis (BS) — Boston College, 2006
Submitted to: Boston College. College of Arts and Sciences
Discipline: Biology
Discipline: College Honors Program
Kobayashi(Miura), Mikiko. "Thioredoxin,an anti-oxidant protein,protects mouse embryos from oxidative stress-induced developmental anomalies." Kyoto University, 2002. http://hdl.handle.net/2433/149333.
Повний текст джерелаDutta, Khokon Kumar. "Two distinct mechanisms for loss of thioredoxin-binding protein-2 in oxidative stress-induced renal carcinogenesis." Kyoto University, 2007. http://hdl.handle.net/2433/135665.
Повний текст джерелаDomènech, Guil Alba 1985. "Oxidative stress in toxicity and signaling : Control of cysteine oxidation and reduction by the redoxin systems of fission yeast." Doctoral thesis, Universitat Pompeu Fabra, 2018. http://hdl.handle.net/10803/664636.
Повний текст джерелаSchizosaccharomyces pombe, as all aerobic organisms, needs oxygen to live and have to deal with the side effects of the toxicity associated to oxygen by-products. To maintain intracellular environment, S. pombe has antioxidant systems that are activated fast and in a reversible manner. Depending on the severity of the oxidative stress suffered, S. pombe has two main antioxidant response pathways, Pap1 and Sty1 pathways, for sub-toxic and toxic hydrogen peroxide (H2O2) levels, respectively. These cascades involve sensor proteins that contain cysteine residues called thiol switches, which can switch on and off their activities. Therefore, all the components involved in the antioxidant signaling cascades have to be recycled in order to be ready to act again. For these reason, the reduction systems, thioredoxin and glutathione/glutaredoxin systems, have an essential role as backup systems of the components of the H2O2 signaling redox relays in fission yeast. Along this thesis I have studied the importance of a proper activity of both reduction systems in the recycling of redox proteins to avoid cell toxicity and to assure a normal cell cycle progression. On the other hand, we characterized how thresholds of oxidative stress tolerance are important to trigger signaling or toxicity responses in S. pombe.
Loganathan, Usha R. "Characterization of the thioredoxin system in Methanosarcina mazei." Thesis, Virginia Tech, 2014. http://hdl.handle.net/10919/71334.
Повний текст джерелаMaster of Science
Singh, Komudi. "Oxidant-Induced Cell Death Mediated By A Rho Gtpase In Saccharomyces cerevisiae." Columbus, Ohio : Ohio State University, 2008. http://rave.ohiolink.edu/etdc/view.cgi?acc%5Fnum=osu1227716169.
Повний текст джерелаTan, Shixiong Biotechnology & Biomolecular Sciences Faculty of Science UNSW. "Cellular mechanisms affecting redox homeostasis in response to stress in Saccharomyces cerevisiae." Awarded by:University of New South Wales. Biotechnology & Biomolecular Sciences, 2009. http://handle.unsw.edu.au/1959.4/44627.
Повний текст джерелаBjur, Eva. "Virulence of Salmonella enterica serovar typhimurium and innate antibacterial host responses /." Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-946-7/.
Повний текст джерелаSelles, 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.
Повний текст джерелаProtein 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
Wagner, Caroline. "Estudo de mecanismos de toxicidade do metilmercúrio: papel protetor de flavonóides." Universidade Federal de Santa Maria, 2010. http://repositorio.ufsm.br/handle/1/4419.
Повний текст джерелаMethylmercury (MeHg) is an important environmental toxicant that may cause irreversible neurobehavioral and neuropsychological disorders in humans and experimental animals. The major mechanisms of MeHg-induced toxicity currently being explored are the disruption of intracellular calcium homeostasis, the induction of oxidative stress, inhibition of neuronal Na+/K+ -ATPase activity and change the status of antioxidant systems. In addition, recent data reported the involvement of MeHg toxicity with damage in thioredoxin system. On the other hand, flavonoids have been reported to possess divalent metal chelating properties, antioxidant activities and to readily permeate the blood brain barrier. They can also provide neuroprotection in a wide array of cellular and animal models of neurological diseases, including protection against MeHg toxicity. However, the exact mechanism of MeHg toxicity remain unclear and limited data on the interaction of MeHg with flavonoids are avaliable in literature. In view of this, our study evaluated the mechanisms of MeHg toxicity in vivo and in vitro models and evaluated the performance of different flavonoids: quercetin, quercitrin and rutin in diferent models of MeHg toxicity. Our study showed that MeHg (100 μM) caused lipid peroxidation and reactive oxygen species (ROS) generation in brain cortical slices. Quercitrin and quercetin protected against this toxicity and mitochondria from MeHg (5 μM)-induced ROS generation. In contrast, rutin did not afford a significant protective effect against MeHg (100 μM)-induced lipid peroxidation and ROS production in cortical brain slices. MeHg-generated ROS in cortical slices was dependent upon an increase in intracellular calcium levels. In vivo studies with mice treated during 30 days with MeHg (5mg/Kg) orally, presented a marked increase in toxicity parameters (loss in body weight gain, increased in micronucleis frequencies, nefrotoxicity), decrease in motor system performance (locomotor activity and motor coordination) and spatial memory deficiency as well as alteration in some biochemical parameters (decrease in glutathione peroxidase and Na+/K+ ATPase activity, increase in lipid peroxidation). The co-treatment with quercitrin (10mg/kg) intraperitoneally, decreased the behavior alterations manly by decreased lipid peroxidation levels, maintained the Na+/K+ ATPase and GPx activities. In addition, our study demonstrated, for the first time, that MeHg inhibited the activity of thioredoxin reductase. A single oral MeHg administration (1, 5 and 10 mg/Kg) caused a marked inhibition of kidney TrxR, while in liver a significant inhibition was observed after exposure to 5 and 10 mg/Kg of MeHg (TrxR was determined 24 hours after MeHg). In brain, MeHg did not inhibit TrxR. In vitro results demonstrated that MeHg inhibited brain (0.05 1 μM) , liver (0.05 1 μM) and kidney (0.025 1 μM) TrxR in a dose dependent manner Here, we have extended the characterization of mechanisms associated with the neuroprotective effects of flavonoids quercetin and quercitrin against MeHg-induced toxicity. In addition, we provided novel data establishing that (1) calcium plays a central role in MeHg toxicity, (2) in brain slices MeHg induces mitochondrial oxidative stress both via direct interaction with mitochondria as well as via mitochondria- indirect mechanisms. In addition (3) MeHg (5mg/kg) caused a number of behavioural alterations that are related with an inhibition of cerebelar and cerebral GPx and Na+/K+ ATPase activities and (4) increased in lipid peroxidation.The higly affinity of MeHg to selenol groups of endogenous molecules can lead to (5) inhibition of thioredoxin reductase that can contribute to MeHg toxicity. We conclude that MeHg lead to increase in mitochondria ROS generation that contributes to increase in lipid peroxidation. In addition, the inhibition of important antioxidant enzymes such as GPx ans TrxR can contribute to oxidative damage that can be related to development of behavioral damage. In this view the antioxidant activity of flavonoids quercetin and quercitrin seems to be direct associate with the capacity of flavonoids to confere protection against MeHg toxicity.
O metilmercúrio (MeHg) é um importante agente tóxico ambiental que pode causar desordens neurocomportamentais e neurofisiológicas irreversíveis em humanos e animais experimentais. Os principais mecanismos pelos quais o MeHg induz toxicidade são: a ruptura na homeostase do cálcio intracelular, a indução de estresse oxidativo, a inibição da atividade da Na+/K+ ATPase neuronal e mudanças nos níveis das enzimas antioxidantes. Adicionalmente, dados recentes relatam o envolvimento do sistema da tiorredoxina como um dos alvos de toxicidade do MeHg. Por outro lado, os flavonóides possuem propriedades quelantes para metal divalente, atividade antioxidante e são permeáveis a barreira cérebro-sangue. Além disso, eles podem oferecer neuroproteção a uma variedade de modelos animais e celulares de doenças neurológicas, incluindo proteção contra a toxicidade do MeHg. Considerando que o exato mecanismo pelo qual o MeHg exerce toxicidade permanece desconhecido e que poucos e controversos dados sobre a interação do MeHg com flavonóides são encontrados na literatura, este estudo avaliou os mecanismos de toxicidade do MeHg em modelos in vitro e in vivo bem como, o desempenho de diferentes flavonóides: quercetina, quercitrina e rutina em diferentes modelos de toxicidade induzidos pelo MeHg. Nosso estudo mostrou que o MeHg (100μM) causou aumento na peroxidação lipídica e na produção de espécies reativas de oxigênio (EROs) em fatias de córtex de ratos. Os flavonóides quercitrina (25 μg/mL) e quercetina (5, 10 e 25 μg/mL) protegeram contra esta toxicidade, e contra o aumento de ERO produzidas pelo MeHg (5μM) nas mitocôndrias. Diferentemente, o flavonóide rutina não obteve efeito protetor contra a indução da peroxidação lipídica e produção de ERO induzidas pelo MeHg em fatias corticais de cérebro. O aumento na produção de ERO, geradas pelo MeHg, foi dependente do aumento dos níveis intracelulares de cálcio (artigo 1). Já, estudos in vivo com camundongos tratados oralmente com MeHg (5mg/kg), durante 30 dias, mostraram um marcado aumento nos parâmetros de toxicidade (diminuição no ganho de peso, aumento na freqüência de micronúcleos e nefrotoxicidade), diminuição no desempenho do sistema motor (atividade locomotora e coordenação motora), e deficiência na memória espacial, bem como alterações em vários parâmetros bioquímicos (diminuição na atividade da glutationa peroxidase (GPx) e Na+/K+ ATPase e aumento na peroxidação lipídica). O co-tratamento com quercitrina (10mg/kg) pela via intraperitoneal, diminuiu as alterações comportamentais principalmente por diminuir os níveis de peroxidação lipídica e manter a atividade da GPx e da Na+/K+ ATPase iguais aos níveis do controle (manuscrito 1). Além disso, nosso estudo demonstrou, pela primeira vez, que o MeHg inibe a atividade da tiorredoxina redutase (TrxR). Uma única administração oral de MeHg (1, 5, 10 mg/kg), causou uma marcada inibição na atividade da TrxR renal, enquanto no fígad observou-se uma inibição significativa após exposição a 5 e 10 mg/kg (a atividade da TrxR foi determinada 24 horas após a administração de MeHg). No cérebro, o MeHg não inibiu a atividade da TrxR in vivo (artigo 2). Já os resultados in vitro revelaram que o MeHg causou uma inibição concentração dependente na atividade da enzima TrxR isolada de cérebro (0,05 1 μM) fígado (0,05 - 1 μM) e rim (0,025 1 μM). Assim, nós ampliamos a caracterização dos mecanismos associados com os efeitos neuroprotetores dos flavonóides quercetina e quercitrina na toxicidade induzida pelo MeHg. Adicionalmente, outros dados sobre a toxicidade do MeHg, foram obtidos, tais como: (1) o cálcio desempenha um papel central na toxicidade do MeHg, (2) em fatias de cérebro de ratos o MeHg induz estresse oxidativo mitocondrial via interação direta com as mitocôndrias, bem como via mecanismos mitocondriais indiretos. Além disso, (3) o MeHg (5mg/kg) pode levar a inúmeras alterações comportamentais que podem estar relacionadas à inibição da atividade das enzimas GPx e Na+/K+ ATPase e (4) aumento na peroxidação lipídica. A alta afinidade do MeHg por grupos selenóis das moléculas endógenas pode levar (5) a inibição da TrxR o que pode contribuir para a toxicidade do MeHg. Podemos concluir que o MeHg leva a um aumento na produção de ERO pelas mitocôndrias, o que contribui para um aumento na peroxidação lipídica induzida pelo MeHg. Além disso, a inibição de importantes enzimas antioxidantes como a GPx e a TrxR podem contribuir para aumentar o dano oxidativo, que parece estar relacionado com o aparecimento dedanos comportamentais. Desta forma a atividade antioxidante dos flavonóides quercetina e quercitrina parece estar diretamente associada à capacidade destes compostos emproteger contra a toxicidade do MeHg.
Canesi, Fanny. "Les peptides mimétiques de la Thiorédoxine-1 : nouvelle stratégie thérapeutique pour les maladies cardiovasculaires." Thesis, Sorbonne université, 2018. http://www.theses.fr/2018SORUS500.
Повний текст джерелаOxidative stress and inflammation play a pathogenic role in atherosclerosis. Thioredoxin-1 (Trx-1) is an anti-oxidative, anti-inflammatory protein with atheroprotective effects. However, in vivo cleavage of Trx-1 generates a truncated pro-inflammatory protein, Trx-80, which compromises the therapeutic use of Trx-1. The aim of my thesis is to characterize a new therapeutic strategy based on Trx-mimetic peptides (TxMP) for the treatment of atherosclerosis. We synthesized a small peptide based on the active site of Trx-1 named CB3. Firstly, CB3 was validated on cultured peritoneal murine macrophages (cellular viability, anti-oxidant and anti-inflammatory responses). Secondly, the atherosclerotic mouse model (ApoE2.Ki) fed a high fat diet was intraperitoneally injected with CB3 to measure their anti-oxidant, anti-inflammatory and anti-atherogenic effects. Our results clearly showed that, similar to the full length Trx-1, CB3 exerts protective effects by reducing inflammation and oxidative stress in macrophages and in ApoE.Ki mice. The atheroprotective effect of CB3 opens promising therapeutic approaches for treatment of atherosclerosis
Hossain, Akter. "Studies on Redox-proteins and Cytokines in inflammation and Cancer." Doctoral thesis, Linköping : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-8798.
Повний текст джерелаJohansson, Catrine. "Biochemical properties of human glutaredoxins /." Stockholm : Karolinska institutet, 2004. http://diss.kib.ki.se/2004/91-7349-874-2/.
Повний текст джерелаComparsi, Bruna. "Efeitos da n-acetilcisteína sobre a toxicidade do ditelureto de difenila no encéfalo de camundongos." Universidade Federal de Santa Maria, 2015. http://repositorio.ufsm.br/handle/1/4496.
Повний текст джерелаThe diphenyl ditelluride (PhTe)2 is one of the most toxic organic compounds of tellurium which can make their use unsafe. The mechanism(s) involved in (PhTe)2 toxicity is(are) elusive, but thiol oxidation of critical proteins are important targets. Consequently, the possible remedy of its toxicity by thiol-containing compounds is of experimental and clinical interest. Therefore, this study aimed to evaluate the toxicity of in vivo exposure to (PhTe)2 from oxidative stress biomarkers and behavioral parameters in adult mice and the possible protective effect of N-acetylcysteine (NAC). They evaluated parameters of oxidative stress and behavior in mice. In order to alleviate the toxicity, NAC was administered before (3 days) and simultaneously (PhTe)2 (7 days). Mice were separated into six groups receiving daily injections of (1) Potassium phosphate buffer (TFK) (2.5 ml/kg, intraperitonealy (i.p.)) plus canola oil (10 ml/kg, subcutaneously (s.c.)), (2) NAC (100 mg/kg, i.p.) plus canola oil s.c., (3) TFK i.p. plus (PhTe)2 (10 μmol/kg, s.c.), (4) TFK i.p. plus (PhTe)2 (50 μmol/kg, s.c.), (5) NAC plus (PhTe)2 (10 μmol/kg, s.c.), and (6) NAC plus (PhTe)2 (50 μmol/kg, s.c.). Treatment with (PhtE) started on day 2 of treatment with NAC. The results demonstrate that (PhTe)2 induced behavioral changes in locomotor activity at a concentration of 50 μmol/kg and NAC did not change the effect of (PhTe)2. Motor coordination and lift the bar were compromised and both showed severe motor abnormalities in test animals independent of concentration of (PhTe)2 . The (PhTe)2 also inhibited important selenoenzymes, thioredoxin reductase (at concentrations of 10 μmol/kg and 50 μmol/kg) and glutathione peroxidase (at concentration of 10 μmol/kg) but produced little or no effect on the antioxidant activity of catalase and glutathione reductase. Contrary to expectation, the co-administration of NAC did not protect against deleterious effects (PhTe)2. It was possible to establish high sensitivity of brain tissue compared to the damage (PhTe)2. Other low molecular weight thiols must be investigated to determine whether they may or may not be effective against ditellurides.
O ditelureto de difenila (PhTe)2 é um dos compostos orgânicos de telúrio mais tóxicos, o que pode tornar seu emprego pouco seguro. O mecanismo envolvido na toxicidade do (PhTe)2 ainda é incerto, mas a oxidação de tióis em proteínas são alvos importantes. A partir disso, compostos contendo tiol possívelmente poderiam solucionar ou minimizar a sua toxicidade. Portanto, este estudo teve como objetivo avaliar a toxicidade da exposição in vivo ao (PhTe)2 a partir de biomarcadores de estresse oxidativo e parâmetros comportamentais em camundongos adultos e o possível efeito protetor da N-acetilcisteína (NAC). Foram avaliados parâmetros de estresse oxidativo e comportamentais em camundongos. A fim de mitigar a toxicidade, foi administrado NAC antes (3 dias) e, simultaneamente ao (PhTe)2 (7 dias). Os camundongos foram separados em seis grupos que receberam injeções diárias de (1) Tampão fosfato de potássio (TFK) (2.5 ml/kg, intraperitonealmente (i.p.)) mais óleo de canola (10 ml/kg, subcutaneamente (s.c.)), (2) NAC (100 mg/kg, i.p.) mais óleo de canola s.c., (3) TFK i.p. mais (PhTe)2 (10 μmol/kg, s.c.), (4) TFK i.p. mais (PhTe)2 (50 μmol/kg, s.c.), (5) NAC mais (PhTe)2 (10 μmol/kg, s.c.), e (6) NAC mais (PhTe)2 (50 μmol/kg, s.c.). O tratamento com (PhTe)2 começou no quarto dia de tratamento com NAC. Os resultados demonstram que (PhTe)2 induziu alterações comportamentais na atividade locomotora na concentração de 50 μmol/kg e a NAC não modificou o efeito do (PhTe)2. A coordenação motora e a força de sustentação na barra foram comprometidas e ambas revelaram alterações motoras graves nos animais testados independente da concentração de (PhTe)2. O (PhTe)2 também inibiu selenoenzimas importantes, tiorredoxina redutase (nas concentrações de 10 μmol/kg e 50 μmol/kg) e glutationa peroxidase (na concentração de 10 μmol/kg), mas produziu mínimo ou nenhum efeito sobre a atividade antioxidante da catalase e glutationa redutase. Contrariamente ao esperado, a co-administração com NAC não protegeu contra os efeitos deletérios do (PhTe)2. Foi possível estabelecer grande sensibilidade do tecido cerebral frente aos danos causados pelo (PhTe)2. Outros tióis de baixo peso molecular devem ser investigados para determinar se eles podem ou não ser eficazes contra diteluretos.
Conterato, Greicy Michelle Marafiga. "Envolvimento do sistema da tiorredoxina nas alterações induzidas pelo chumbo in vitro e in vivo: implicações na toxicidade do chumbo." Universidade Federal de Santa Maria, 2011. http://repositorio.ufsm.br/handle/1/4445.
Повний текст джерелаOxidative stress is an important molecular mechanism of lead (Pb) toxicity. The thioredoxin system (selenoenzyme thioredoxin reductase-TrxR, thioredoxin protein- Trx and NADPH) is essential for the antioxidant defense and cellular redox control. In our previous study, it was showed that cytosolic renal TrxR1 activity of rats increased after acute and long-term exposure to Pb and this was the only parameter that changed after both exposures to low Pb doses. Then, it was suggested that TrxR1 could operate in the early defense against Pb toxicity and it could also be used as a bioindicator of early effects of Pb. Thus, the main objective of this thesis was to investigate the role of thioredoxin system in Pb-induced changes, evaluating: I) in vitro the activity of purified TrxR1, as well as the activity and the protein expression of TrxR1 and Trx1 in renal HEK 293 culture cells exposed to Pb; II) in vivo, the effects of Pb exposure in rats and in occupationally-exposed humans on renal (only in rats) and blood TrxR1 activity (both rats and humans), comparing these effects to oxidative stress parameters, as well as to classical bioindicators of Pb effect and exposure. The results of the in vitro study showed that lead is a less potent inhibitor of the purified TrxR1 activity (IC50 = 0.27 TM) than its structural homologous glutathione reductase (IC50 = 0.048 TM). TrxR1 inhibition was independent on the selenocysteine residue of the active site and was reversible by bovine serum albumin and by the EDTA chelating. TrxR1 inhibition also occurred in HEK 293 cells exposed to the highest Pb acetate concentration (60 TM), without alterations in protein expression. However, under glutathione (GSH) depletion after pre-incubation of cells with L-buthionine-[S,R]-sulfoximine (BSO) and further exposure to Pb, the activity and expression of both TrxR1 and Trx1 increased in the absence of cytotoxicity and of changes in GR and glutathione S-transferase activities, which indicates Trx system as an important protective mechanism against Pb toxic effects in GSH-depleted cells. On the other hand, blood TrxR1 activity did not change either after acute exposure of rats or long-term exposure of humans to Pb. However, the increase of renal TrxR1 activity in rats exposed to the highest dose of Pb acetate (25 mg/kg) occurred concomitantly with the increase of blood and renal Pb levels over time (6, 24 e 48 h), whereas the erythrocyte δ-ALA-D inhibition, which is a classical indicator of Pb effects, occurred after 6 h of exposure and the activity was further recovered (at 24 and 48 h). Moreover, the increase of renal TrxR1 activity occurred without renal histopathologycal damage, which corroborates the increase of this enzyme as an early event of Pb toxicity. Overall, the results of the current study point out the thioredoxin system as a target for Pb, but mainly as a protective mechanism against Pb toxicity. However, the absence of changes in blood TrxR1 activity in Pb-exposed animals and humans indicates that this enzyme is not an appropriate bioindicator of the toxic effects of Pb in exposed populations.
O estresse oxidativo é um importante mecanismo molecular da toxicidade do chumbo (Pb). O sistema da tiorredoxina (selenoenzima tiorredoxina redutase -TrxR, proteína tiorredoxina -Trx e NADPH) é essencial na defesa antioxidante e no controle redox celular. Em nosso estudo prévio, foi demonstrado que a atividade da enzima TrxR1 (citosólica) renal de ratos aumentou na exposição aguda e prolongada ao Pb, sendo o único parâmetro alterado em ambas exposições a doses baixas de Pb. Assim, foi sugerido que a TrxR1 atuaria precocemente na defesa contra a toxicidade do metal, podendo também ser utilizada como um bioindicador dos efeitos precoces do Pb. Assim, o objetivo geral desta tese foi investigar o papel do sistema da tiorredoxina nas alterações induzidas pelo Pb, avaliando: I) in vitro a atividade da TrxR1 purificada, bem como a atividade e expressão protéica da TrxR1 e Trx1 em culturas de células renais HEK 293 expostas ao Pb e II) in vivo, os efeitos do Pb em ratos e em humanos ocupacionalmente expostos ao Pb sobre a atividade da TrxR1 renal (somente em ratos) e sanguínea (ratos e humanos), comparando esses efeitos com parâmetros de estresse oxidativo, bem como com indicadores clássicos de efeito e de exposição ao Pb. Os resultados do estudo in vitro mostraram que a atividade da enzima TrxR1 purificada foi inibida pelo Pb (IC50 = 0.27 TM) de forma menos potente que a sua homóloga estrutural glutationa redutase (IC50 = 0.048 TM). Essa inibição foi independente do resíduo de selenocisteína do sítio ativo da TrxR1 e foi revertida pela albumina sérica bovina e pelo quelante EDTA. A inibição da TrxR1 também ocorreu em células HEK 293 expostas à maior concentração de acetato de Pb (60 TM), sem alterações na expressão protéica. Entretanto, quando os níveis celulares de glutationa (GSH) foram depletados por pré incubação das células com L-butionina-[S,R]-sulfoximina (BSO) e posterior exposição ao Pb, a atividade e a expressão da TrxR1 e da Trx1 aumentaram na ausência de citotoxicidade e de alterações nas atividades da GR e glutationa S-transferase, apontando esse sistema como um importante mecanismo contra a toxicidade do Pb em células sob depleção de GSH. Por outro lado, a atividade da TrxR1 sanguínea não alterou na exposição aguda de ratos e prolongada de humanos ao Pb. No entanto, o aumento da atividade da TrxR1 renal em ratos expostos à maior dose de acetato de Pb (25 mg/kg) foi concomitante com o aumento dos níveis sanguíneos e renais de Pb ao longo do tempo (6, 24 e 48 h), enquanto que a inibição da enzima δ-ALA-D eritrocitária, um indicador clássico de efeito do Pb, ocorreu após 6 h de exposição, sendo sua atividade restabelecida posteriormente (24 e 48 h). Além disso, o aumento da atividade da TrxR1 renal ocorreu sem danos histopatológicos renais, confirmando essa alteração como um evento precoce da toxicidade do Pb. Em geral, os resultados do presente estudo apontam o sistema da tiorredoxina como alvo do Pb, mas principalmente como um mecanismo de proteção contra o metal. Entretanto, a ausência de alterações na atividade da TrxR1 sanguínea em animais e humanos expostos ao Pb, indica que essa enzima não é um bioindicador adequado dos efeitos tóxicos do Pb em populações expostas.
Le, Clanche Solenn. "Implication du système Thiorédoxine des chondrocytes humains soumis à un stress glucosé, en hypoxie et en normoxie : effets du Resvératrol." Thesis, Sorbonne Paris Cité, 2015. http://www.theses.fr/2015USPCB131.
Повний текст джерелаOsteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation, inflammation of synovial membrane and subchondral bone remodelling. Under physiological conditions, chondrocytes - the only cell type found in cartilage - are under hypoxia (around 2% of oxygen). As cartilage is an avascular tissue, an oxygen gradient is established from the superficial to the deeper layers. During OA development, cartilage degradation is responsible for a break in this gradient; consequently, cells from the deepest layers are exposed to higher oxygen concentrations inducing modifications in cell metabolism leading to their dysfunction. Metabolic syndrome (MetS) is defined by a cluster of factors (impairment of glucose and lipid metabolism, vascular dysfunctions…) leading to cardiovascular diseases and type 2 diabetes development. Recently, a link between OA and MetS has been suggested, introducing a notion of metabolic OA. We have focused our study on the link between OA, MetS and oxidative stress induced by high glucose concentrations. In the first part of this study, we have determined the in vitro effects of 25 mM glucose on an immortalized human chondrocyte cell line (T/C28a2), under hypoxia (2% oxygen) and normoxia (21% oxygen). We demonstrated that 25 mM glucose induced radical oxygen species (ROS) and nitric oxide production, caspase 3 activation, interleukin 6 (IL-6) production, decrease in lysyl oxidase (LOX) activity (involved in type II collagen crosslinks), and activation of the thioredoxin (Trx) system. Trx system is an endogenous anti-oxidant system, composed by thioredoxin, thioredoxin reductase (TR) and Txnip; it is involved in cellular homeostasis by reducing oxidized proteins, thereby controlling cellular redox environment. Effects of 25 mM glucose have been observed under both oxygen conditions; nevertheless, cellular response under normoxia underwent earlier than under hypoxia. We have also highlighted Trx-1 as a negative regulator of IL-6 production through p38MAPK signalling pathway. In the second part of this study, we have focused our work on the effects of the addition of an exogenous antioxidant, i.e. resveratrol, on the modifications induced by 25 mM glucose. Indeed, resveratrol (3,4’,5-trihydroxystilbene) is a polyphenol of the stilbene family, known for its multiple anti-inflammatory, anti-oxidative, anti-diabetes and anti-cancer properties. We have observed that 25 μM resveratrol was able to decrease deleterious effects induced by 25 mM glucose. However, resveratrol bioavailability is very low, avoiding its use in human therapeutic strategy. Consequently, in the third part of this study, we have developed new galenic formulations of resveratrol, i.e. nano-emulsions (NEs) and determined their effects on a bovine aortic endothelial cells (BAEC) model, on T/C28a2 cells and also on primary cultures of human chondrocytes from osteoarthritic cartilages. One of our NEs was able to increase resveratrol intracellular passage in both cellular models, and to increase the protective effects of resveratrol against oxidative stress. This NE was also efficient in the normalization of LOX activity in osteoarthritic chondrocytes. To conclude, we have demonstrated that 25 mM glucose induced deleterious effects on chondrocytes of the T/C28a2 cell line, and that an exogenous supply in resveratrol allowed to counteract these effects. Development of a new galenic formulation of resveratrol opens new interesting prospects in human therapeutic strategy against OA associated with MetS
Zahid, Abderrakib. "Mécanismes cellulaires et moléculaires régissant le métabolisme des semences de céréales : rôle du réseau rédoxines-système antioxydant dans la prédiction de la qualité germinative." Thesis, Toulouse, INPT, 2010. http://www.theses.fr/2010INPT0130/document.
Повний текст джерелаA better understanding of the physiology of seed cereal constitutes certainly a means to improve and develop new varieties capable of corresponding to the actual economic and ecological needs. Redoxins are interesting markers to apprehend the technological and germinative quality of wheat seed in particular. The screening of data banks allowed isolating isoforms of these redoxins. This study confirmed the implication of thioredoxins in the reduction of storage proteins in wheat and corn seeds. It allowed to bring to light another role of some thioredoxins h isoforms in the formation of high molecular weights polymers. The inhibition of the expression of genes by DNA interference shows that thioredoxins and glutaredoxins are involved in the protection against oxidative stress in wheat. Also, the application of a biotic stress simulated by laminarin allowed to discriminate the implication of various stress markers, and to highlight in particular that the 1-Cys-Prx can be considered as an indicator of the redox state of the grain during germination and seedling. The implementation of a simple and effective method of transformation of cereal via Agrobacterium constitutes a means to understand more on the role of these redoxins in the management of the stress, and the possible consequences on the technological quality of the seed
Staerck, Cindy. "Etude de la réponse au stress oxydatif de Scedosporium apiospermum, un champignon filamenteux associé à la mucoviscidose." Thesis, Angers, 2017. http://www.theses.fr/2017ANGE0058/document.
Повний текст джерелаCystic fibrosis (CF) is the most common genetic disease in Caucasian populations. The Scedosporium genus ranks the second among the filamentous fungi colonizing the airways of CF patients. In the respiratory tract, colonizations/infections lead to the recruitment of phagocytes which produce an oxidative stress, usually deleterious for pathogens. To defend themselves, pathogens have developed protective antioxidant systems, especially various enzymes. This thesis aimed to study the oxidative stress response in Scedosporium species. First, capacity of several Scedosporium isolates to germinate upon oxidative stress conditions was evaluated. Then, thirty-three genes potentially involved in protection against the oxidative stress were identified. Their overexpression in response to oxidants and in co-cultures with phagocytes suggested a crucial role, especially for one catalase, one peroxiredoxin and the two thioredoxin reductases. A mutant defective for the gene encoding a superoxide dismutase (SOD) anchored to the cell wall and specific for the conidia was produced. Auranofin, a thioredoxin reductase inhibitor, exhibits little anti-Scedosporium activity and an additive effect with triazole drugs. An ELISA was developed for serodiagnosis of scedosporiosis, using recombinant proteins derived from one catalase and a Cu/Zn-SOD. This sensitive and specific assay allows to differentiate Scedosporium infections from Aspergillus fumigatus infections and Scedosporium colonizations. Finally, these results indicate a crucial role of antioxidant enzymes in Scedosporium species, which could therefore be considered as virulence factors and as possible new therapeutic targets
Peroja, P. (Pekka). "Oxidative stress in diffuse large B-cell lymphoma and follicular lymphoma, and TP53 mutations and translocations of MYC, Bcl-2 and Bcl-6 in diffuse large B-cell lymphoma." Doctoral thesis, Oulun yliopisto, 2018. http://urn.fi/urn:isbn:9789526218595.
Повний текст джерелаTiivistelmä Diffuusi suurisoluinen B-solulymfooma (DLBCL) ja follikulaarinen lymfooma (FL) ovat kaksi yleisintä lymfoomaa länsimaissa. DLBCL on aggressiivinen syöpä, joka reagoi hyvin hoitoihin, jopa 75 % paranee. Kuitenkin potilailla, joilla syöpä uusiutuu hoitojen jälkeen tai etenee hoidon aikana, on erittäin huono ennuste, noin 10-20 % näistä potilaista voidaan parantaa. FL on hyväennusteinen lymfooma, joka yleensä reagoi hyvin hoitoihin. Mediaani elossaoloaika kaikilla FL potilailla on yli 15 vuotta taudin toteamisesta. Osalla potilaista FL kuitenkin on aggressiivisempo. Oksidatiivinen stressin, TP53- mutaatioiden, MYC, Bcl-2 ja Bcl-6 -translokaatioiden on todettu olevan huonoon ennusteeseen yhteydessä olevia tekijöitä monissa syövissä, kuten lymfoomissa. Tämä väitöskirja tutki oksidatiivisen stressin ja hapetus-pelkistys reaktioon liittyvien entsyymien osuutta R-CHOP-hoidetuissa DLBCL:ssa ja FL:ssa immunohistokemian (IHC) avulla. DLBCL:ssa tutkittiin lisäksi TP53 mutaatioita, MYC, Bcl-2 ja Bcl-6 translokaatioiden roolia taudin kulussa. Korkea ekspressio oksidatiivisen stressin merkkiainetta nitrotyrosiinia ja antioksidantti thioredoksiinia olivat yhteydessä huonoon ennusteeseen DLBCL:ssa. FL:ssa runsas ilmentyminen antioksidativiisiin entsyymeihin kuuluvia peroksiredoksiineja olivat yhteydessä hyvään ennusteeseen. TP53 mutaatiot LSH ja L3 alueella ja Bcl-2 -translokaatiot yhdessä olivat yhteydessä huonoon ennusteeseen DLBCL:ssa. Kaikki TP53-mutaatiot eivät olleet assosioituneet huonoon ennusteeseen. DLBCL:ssa Bcl-2 ja MYC –proteiinien runsas ilmentyminen IHC:llä arvioituna liittyi huonoon ennusteeseen. Tulosten perusteella solujen hapetus-pelkistystilaa säätelevillä entsyymeillä voi olla dualistinen rooli, osittain suojeleva ja osittain vahingoittava lymfoomissa. TP53 -mutaatioilla voi olla ennusteellista merkitystä, mutta tämä vaatii lisää tutkimuksia
DOMINGOS, Fernanda de Castro. "Caracterização Molecular e Expressão Heteróloga de um cDNA Codificante para Tiorredoxina do fungo patogênico humano Paracoccidioides brasiliensis." Universidade Federal de Goiás, 2006. http://repositorio.bc.ufg.br/tede/handle/tde/1275.
Повний текст джерелаThe temperature-dependent dimorphic fungus Paracoccidioides brasiliensis is the etiological agent of Paracoccidioidomycosis (PCM), a human systemic mycosis highly prevalent in countries of Latin America. P. brasiliensis is subjected to different insults from human host, such as oxidative stress caused by reactive oxygen species produced by the host during the infection. Thioredoxin (TRX) is an intracellular redox protein that is required to maintain redox homeostasis in response to both reductive and oxidative stress conditions in several organisms. We report here the characterization of a 811 bp cDNA Pbtrx1, encoding a PbTRX1 of 116 amino acids, with a predicted molecular mass of 12 kDa and pI 5.2. This putative protein presented one highly conserved active site motif (WCGPC) between TRXs from several organisms. The phylogenetic analysis performed with PbTRX1 and TRXs from other organisms, putted P. brasiliensis in the fungi clade. We also performed the prediction of the secondary structure of PbTRX1 that shows a pattern characteristic of the open twisted alpha/beta, similar to TRX secondary structures described in other fungus. In order to obtain the recombinant PbTRX1, the expression construct pGEX-4T-3-trx1 was introduced into Escherichia coli cells and the expression and purification of the recombinant protein was obtained. The recPbTRX1 and PbTRX1 from yeast cells extract were found to catalyze the reduction of insulin. However the PbTRX1 from yeast cells extract treated with H2O2 showed highly insulin reduction activity than the yeast cells no treated. PbTRX1 was detected by Western blotting in the extracts from yeast cells growth and from mycelium to yeast transition. The yeast cells growth was significantly inhibited by H2O2; however the mycelium to yeast transition was little affected by this oxidant. Semi-quantitative RT-PCR was employed to analysis the expression of Pbtrx1 gene in response to H2O2. The level of Pbtrx1 transcripts was higher in yeast cells treated with H2O2 than in yeast cells no treated. To realize how P. brasiliensis deals with oxidative stress is essential to understand the mechanisms involved in its survival in the host. It may be possible that PbTRX1 enhances survival of P. brasiliensis in the host, protecting the fungus against the reactive oxygen species and allowing, in this way, the progress of the infection.
O fungo termodimórfico, Paracoccidioides brasiliensis, é o agente etiológico da paracoccidioidomicose (PCM), uma micose sistêmica humana, com alta prevalência na América Latina. No hospedeiro humano, o fungo P. brasiliensis está sujeito a vários insultos, tais como o estresse oxidativo causado pelas espécies reativas de oxigênio, que são produzidas pelas células de defesa do hospedeiro durante a infecção. A tiorredoxina (TRX) é proteina redox intracelular que participa da manutenção da homeostase redox da célula, tanto em condições de estresse oxidativo quanto redutor. Neste trabalho apresentamos a caracterização de um cDNA de 811 pb, designado como Pbtrx1, que codifica para uma proteína, PbTRX1, de 116 resíduos de aminoácidos com massa molecular predita de 12 kDa e pI de 5,2. PbTRX1 apresentou um motivo de sítio ativo conservado (WCGPC) entre as TRXs de vários organismos. Análise filogenética com PbTRX1 e TRXs de outros organismos colocou P. brasiliensis no clado de fungos. Foi também realizada a predição da estrutura secundária da PbTRX1, que apresentou um padrão característico formado por cadeias-β que estão envolvidas por α-hélices. Para obter a proteína recombinante, recPbTRX1, foi realizada a construção do pGEX-4T-3-trx1 e este foi introduzido nas células de Escherichia coli. Assim, a expressão e purificação da proteína recombinante foi obtida. A proteína recPbTRX1 e a PbTRX1, presente no extrato protéico de células leveduriformes, apresentaram atividade redutora de insulina. Entretanto, a PbTRX1 presente no extrato protéico de células leveduriformes tratadas com H2O2, mostrou maior atividade redutora de insulina quando comparada com extrato de células leveduriformes não tratadas. A PbTRX1 foi detectada, por Western blotting, em extratos de células leveduriformes em crescimento e durante a transição de micélio para levedura. O crescimento das células leveduriformes foi inibido por H2O2, entretanto a transição de micélio para levedura foi pouco afetada por este oxidante. A técnica de RT-PCR semi-quantitativo foi empregada para análise da expressão do Pbtrx1 em resposta ao H2O2. O nível de transcritos de Pbtrx1 foi maior nas células leveduriformes tratadas com H2O2 do que nas células não tratadas. Para compreender como P. brasiliensis lida com estresse oxidativo é essencial entender os mecanismos envolvidos em sua sobrevivência no hospedeiro. É possível que PbTRX1 aumente a sobrevivência de P. brasiliensis no hospedeiro, protegendo o fungo contra espécies reativas de oxigênio e, desta maneira, permitindo o progresso da infecção.
Monteiro, Maria Beatriz Camargo de Almeida. "Polimorfismos nos genes que codificam a glutationa peroxidase-4, a tiorredoxina e a proteína de interação com a tiorredoxina modulam a susceptibilidade à doença renal em portadores de diabetes mellitus tipo 1." Universidade de São Paulo, 2012. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-25042012-092352/.
Повний текст джерелаINTRODUCTION: there is evidence suggesting that genetic factors are involved in the susceptibility to the development of renal complications in patients with type 1 diabetes mellitus (DM1). Several genes related to the mechanisms of hyperglycemia-induced cell damage have been investigated. Oxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. Thus, genes that encode enzymes involved in endogenous antioxidant pathways may be candidates for conferring risk or protection against renal complications. The glutathione, glutaredoxin, and thioredoxin systems and transketolase enzyme are important mechanisms of cellular defense against oxidative stress. OBJECTIVES: to evaluate the association between the following single nucleotide polymorphisms (SNPs) and renal disease in type 1 diabetic patients: -2030 T/G (rs34071297) and +718C/T (rs713041) in the gene encoding glutathione peroxidase 4 (GPX4); -3310 G/C (rs10427424) in the gene encoding glutathione synthetase (GSS); -247 A/G (rs2978668) in the gene encoding glutathione reductase (GSR); -2763 A/G (rs6556885) in the gene encoding glutaredoxin (GLRX); -224 T/A (rs2301242) in the gene encoding thioredoxin (TXN); +402 T/C (rs7211) in gene encoding thioredoxin interacting protein (TXNIP); -192 G/A (rs3788319) in the gene encoding thioredoxin reductase 2 (TXNRD2); - 3787 T/G (rs7637934) and -1410 T/C (rs11130365) in the gene encoding transketolase (TKT). MATERIALS AND METHODS: 443 patients (192 males and 251 females) with type 1 diabetes duration > 10 years were grouped according to presence or absence of the following complications: (1) overt diabetic nephropathy (DN) defined by persistent macroalbuminuria to proteinuria; (2) established diabetic nephropathy (EDN), defined by persistent macroalbuminuria or proteinuria or estimated glomerular filtration rate (RFGe) < 60 mL/min/1.73 m2 or patients under renal replacement therapy and (3) RFGe or < 60 mL/min/1.73 m2. Pearsons 2 test was performed to compare the genotype frequencies and magnitude of association was estimated using odds ratios (OR). Adjusted OR was estimated by logistic regression for possible confounders (sex, age at diagnosis, diabetes duration, HbA1C, cholesterol and triglyceride concentrations and the presence of hypertension). Nondiabetic subjects were also included. RESULTS: The presence of at least one T polymorphic allele of the SNP GPX4 +718 C/T was protective against EDN (OR = 0.41, CI 95% 0.19- 0.83, p= 0.0146) and against overt DN (OR=0.37; IC 95% 0.15-0.85; p= 0.021) in the male population even after adjustment for possible confounders. The presence of two polymorphic alleles of the SNP TXN -224 T/A conferred independent risk for the presence of overt DN in the female population after adjustment for possible confounders (OR = 4.06, CI 95% 1.59- 10.6, p= 0.0035). The TT genotype for the SNP TXNIP +402 T/C was more frequent in patients with type 1 diabetes compared to nondiabetic controls. The genotype CC of the SNP TXNIP +402 T/C was protective against EDN in male population even after adjustment for possible confounders (OR=0.45; IC 95% 0.22-0.91; p= 0.02) CONCLUSIONS: The SNPs GPX4 +718C/T (rs713041), TXN -224 T/A (rs2301242) and TXNIP +402T/C (rs7211) modulate the risk for renal disease in the studied population of type 1 diabetes patients
Urban, Constantin. "Thioredoxin Peroxidase des Humanpathogens Candida albicans ein differenziell lokalisiertes und multifunktionelles Enzym /." [S.l. : s.n.], 2004. http://www.bsz-bw.de/cgi-bin/xvms.cgi?SWB11730038.
Повний текст джерелаKneeshaw, Sophie. "Molecular mechanisms of redoxin-mediated signalling in plant immunity." Thesis, University of Edinburgh, 2016. http://hdl.handle.net/1842/18754.
Повний текст джерелаLee, Yi-Hwe, and 李怡慧. "Mechanism of oxidative stress-induced Thioredoxin peroxidase II expression." Thesis, 2004. http://ndltd.ncl.edu.tw/handle/14746533653858990155.
Повний текст джерела國立中央大學
生命科學研究所
92
Abstract Thioredoxin peroxidase II (TPx II) is an oxidative stress-inducible enzyme that functions in cell proliferation and differentiation, and protects other proteins from oxidative damage. Arsenic is an environmental pollutant associated with human skin, lung, liver cancers and cardiovascular diseases. Recent studies suggested that arsenic-induced toxicity is associated with the generation of free radicals. This study investigates the mechanism of sodium arsenite (As(III))- and other oxidative stress-induced TPx II expression in murine fibroblast cells (3T3). The results showed that As(III), H2O2, CdCl2 and DPPH dose-dependently induced TPx II protein expression in 3T3 cell. The mRNA level of TPx II were also induced by As(III), H2O2, and DPPH, but not CdCl2. In addition, the phospho-ERK protein level was significantly enhanced in response to As(III) treatment. The As(III)-induced TPx II expression could be dose-dependently abolished by the presence of Rotterlin (PKC δ specific inhibitor); however, Rotterlin showed no effect on H2O2- and DPPH-induced TPx II expression. We further investigated the effect of As(III) on TPx II expression in transcription level. The results showed that a DNA response element located at TPx II promoter 269-169 pair was critical for As(III) inductory effect on TPx II gene expression. The As(III)-induced TPx II expression was further enhanced by another transcriptional factor FKHR that had no effect on H2O2-, CdCl2- and DPPH-induced TPx II expression. These results indicated that the mechanism of As(III) induces TPx II protein expression likely through oxidative stress pathway by which is dependent on FKHR and distinct from that induced by H2O2, CdCl2 and DPPH.
Dolman, Fleur Catherine. "Functional characterisation of plant cytosolic thioredoxins." Thesis, 2010. http://hdl.handle.net/2440/64583.
Повний текст джерелаThesis (Ph.D.) -- University of Adelaide, School of Agriculture, Food and Wine, 2010
Chrysostomou, Constantine. "Investigating cellular responses to mutations in the glutathione and thioredoxin pathways of Escherichia coli." Thesis, 2009. http://hdl.handle.net/2152/ETD-UT-2009-12-706.
Повний текст джерелаtext
Hodková, Anna. "Účinky vybraných přírodních látek na antioxidační systém organismu." Doctoral thesis, 2016. http://www.nusl.cz/ntk/nusl-348470.
Повний текст джерелаTan, Kah Poh. "Nuclear Factor (Erythroid 2-like) Factor 2 (Nrf2) as Cellular Protector in Bile Acid and Retinoid Toxicities." Thesis, 2008. http://hdl.handle.net/1807/17287.
Повний текст джерела