Dissertations / Theses on the topic 'Mitochondrial reactive oxygen species'
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Logan, Angela. "Production of reactive oxygen species in mitochondria and mitochondrial DNA damage." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609201.
Full textHurd, T. R. "Interactions between mitochondrial protein thiols and reactive oxygen species." Thesis, University of Cambridge, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.604824.
Full textLi, Xinyuan. "Mitochondrial Reactive Oxygen Species Mediate Lysophosphatidylcholine-induced Endothelial Cell Activation." Diss., Temple University Libraries, 2015. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/320473.
Full textPh.D.
Lysophosphatidylcholines (LPCs) are a class of pro-inflammatory lipids that play important roles in atherogenesis. LPC activates endothelial cells (ECs) to upregulate adhesion molecules, cytokines and chemokines, which is the initiation step of atherogenesis. However, the mechanisms underlying LPC-triggered EC activation are not fully understood. Previously considered as the toxic by-products of cellular metabolism, mitochondrial reactive oxygen species (mtROS) are recently found to directly contribute to both the innate and adaptive immune responses. Here we tested a novel hypothesis that mtROS serve as signaling mediators for LPC-induced EC activation. Using electron spin resonance and flow cytometry with mtROS-specific fluorescence probe MitoSOX, we found that several LPC species including LPC 16:0, 18:0, and 18:1 induced mtROS in human primary aortic ECs (HAECs). Mechanistically, our analysis using confocal microscopy and Seahorse XF96 mitochondrial function analyzer showed that LPC induced mtROS via increasing mitochondrial calcium-mediated increase of mitochondrial respiration. In addition, we found that mtROS scavenger MitoTEMPO abolished LPC-induced EC activation by downregulating Intercellular adhesion molecule 1 (ICAM-1) in HAECs. Moreover, our analysis with mass spectrometer analysis of histone H3 lysine acetylation and electrophoretic mobility shift assay (EMSA) showed that MitoTEMPO acts by blocking LPC-induced histone H3 lysine 14 acetylation (H3K14ac) and nuclear translocation of pro-inflammatory transcription factor activator protein-1 (AP-1). Remarkably, all the above effects can be inhibited by anti-inflammatory cytokines interleukin (IL-35) and IL-10. Our results indicate that mtROS are responsible for LPC-induced EC activation, which can be inhibited by anti-inflammatory cytokines. MtROS targeting therapies and anti-inflammatory cytokines such as IL-35 may serve as novel therapeutic targets for vascular inflammation and cardiovascular diseases. The studies in this dissertation were supported by grants from the National Institutes of Health (NIH) funded to Dr. Xiao-Feng Yang.
Temple University--Theses
Hinchy, Elizabeth. "How cellular ATP/ADP ratios and reactive oxygen species affect AMPK signalling." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/270029.
Full textCollins, Yvonne. "Regulation of pyruvate dehydrogenase kinase 2 by mitochondrial reactive oxygen species." Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708470.
Full textSanusi, Morufat Olayide Abisola. "Mitochondrial reactive oxygen species signalling and vascular smooth muscle cell senescence." Thesis, University of Leicester, 2016. http://hdl.handle.net/2381/37968.
Full textRogers, Kara Emilie. "Mitochondrial Antioxidants, Protection Against Oxidative Stress, and the Role of Mitochondria in the Production of Reactive Oxygen Species." Diss., The University of Arizona, 2006. http://hdl.handle.net/10150/194490.
Full textSchwarzlander, Markus. "The Response to Mitochondrial Reactive Oxygen Species and Redox Status in Plants." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.504582.
Full textGarlid, Anders Olav. "Mitochondrial Reactive Oxygen Species (ROS): Which ROS is Responsible for Cardioprotective Signaling?" PDXScholar, 2014. https://pdxscholar.library.pdx.edu/open_access_etds/1641.
Full textHansson, Anna. "Cellular responses to respiratory chain dysfunction /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-493-7/.
Full textApostolova, Nadezda. "Mitochondrial role of Apoptosis-Inducing Factor (AIF): Oxidative Phosphorylation and Reactive Oxygen Species." Doctoral thesis, Universitat de València, 2008. http://hdl.handle.net/10803/9775.
Full textLa función proapoptótica del Factor Inductor de Apoptosis (AIF) está biendocumentada, sin embargo su papel fisiológico en la mitocondria es menos conocido.Empleando la metodología de interferencia por ARN, estudiamos si la modulación de laexpresión proteica de AIF en cultivo celular modifica la producción celular de especiesreactivas de oxígeno (ROS). Observamos que el silenciamiento de AIF estaba seguidopor un incremento significativo en los niveles de las ROS. Estas ROS fueronmitocondriales de origen, puesto que el silenciamiento de AIF en células que carecende la cadena de transporte electrónico funcional (ETC) en la mitocondria no llevó a unincremento de ROS. Este incremento fue suficiente para activar el Factor inducible porhipoxia (HIF-1α), efecto que se puede revertir usando los antioxidantes, N-AcetilCisteina y MitoQ, demostrando así la implicación de los ROS en la estabilización deHIF1-α. Los análisis del consumo de oxigeno celular mostraron que las células de AIFsilenciado sufren una disminución en la respiración celular, al nivel del Complejo I de laETC, acompañada por una disminución significativa en la expresión de sus subunidades39 y la 20kDa. Tratamientos con los antioxidantes previamente nombrados mostraronque la tasa de respiración se puede recuperar, no siendo así con la expresión delComplejo I de la ETC. Estudios del estado energético de las células siAIF mostraronque a pesar de la disminución de 30% en la tasa de la respiración celular, estas célulasmantienen niveles normales de ATP, como resultado de un incremento en la capacidadglucolítica y una reducción en la tasa de proliferación. Posteriormente, analizamos laexpresión de la proteína tioredoxina y observamos una disminución significativa en laisoforma mitocondrial, la tioredoxina 2 (Trx2), aunque los análisis preliminares de coinmunoprecipitacióny proteómica no mostraron la existencia de una correlacióndirecta entre las proteínas AIF y Trx2.Concluyendo, nuestros resultados sugieren que el defecto de la respiración celular esposterior al defecto en el Complejo I, probablemente como consecuencia al daño de laETC por ROS. Esta observación apunta a un papel integrador de AIF en la mitocondria,como modulador del estatus redox y necesario para el ensamblaje del Complejo I.
Maranzana, Evelina Susana Beatriz <1971>. "Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from Complex I." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6601/.
Full textBrouillette, Marc James. "Mechanical stimulation of cartilage induces mitochondrial reactive oxygen species production mediating metabolic responses." Diss., University of Iowa, 2015. https://ir.uiowa.edu/etd/5428.
Full textLiu, Bin. "P53 AND REACTIVE OXYGEN SPECIES: A CONVOLUTED STORY." UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_theses/450.
Full textYang, Wen. "Mitochondrial dysfunction and reactive oxygen species metabolism in the aging process of «Caenorhabditis elegans»." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=94989.
Full textLe nématode Caenorhabditis elegans est un organisme modèle qui a été extensivement étudié afin de mieux comprendre les bases de la génétique du vieillissement. Ces études ont mené à l'identification de plusieurs gènes jouant des rôles essentiels dans la détermination de la durée de vie de ce ver rond. La majorité de ces gènes sont exprimés au niveau des mitochondries, des organelles reconnues pour jouer un rôle primordial dans la régulation du métabolisme énergétique et pour être les principales sources des dérivés actifs de l'oxygène (reactive oxygen species, ROS). Ces deux caractéristiques propres aux mitochondries sont reconnues pour être cruciales dans la détermination de la durée de vie. Elles sont d'ailleurs à l'origine d'une hypothèse sur la cause du vieillissement, la théorie du stress oxydatif, qui propose que la génération de ROS par les mitochondries cause le vieillissement en induisant de façon graduelle des dommages oxydatifs aux divers constituants cellulaires. Dans cette étude, nous avons démontré que l'augmentation de la durée de vie observée chez des nématodes mutants pour des gènes mitochondriaux impliqués dans le transport des électrons (i.e. isp-1 and clk-1) ainsi que chez d'autres mutants reconnus pour leur longévité accrue n'est pas reliée à une diminution des dommages oxydatifs. D'autre part, nous avons montré que leur durée de vie n'est pas réduite suite à l'induction d'un stress oxydatif causant divers dommages. Cette étude nous a aussi amené à identifier un nouveau gène, nuo-6 (qm200), codant pour l'orthologue chez le ver de la sous-unité B15 du complexe I de la chaîne de respiration mitochondrial précédemment caractérisée chez les mammifères. La mutation de ce gène résulte en une augmentation de la durée de vie d'une manière similaire à ce qui est observé chez les vers mutants pour le gène isp-1(qm150), qui code pour une sous-unité du complexe III. L'utilisation d
Deng, Ying. "ROLE OF THE REACTIVE OXYGEN SPECIES PEROXYNITRITE IN TRAUMATIC BRAIN INJURY." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/667.
Full textAsh, Catherine Elizabeth. "Functional and molecular mechanisms underlying reduced mitochondrial reactive oxygen species generation under dietary restricted feeding conditions." Thesis, University of Liverpool, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.494167.
Full textRaucci, Frank. "SPHINGOLIPID-INDUCED ACTIVATION OF THE VOLUME-SENSITIVE Cl− CURRENT IS MEDIATED BY MITOCHONDRIAL REACTIVE OXYGEN SPECIES." VCU Scholars Compass, 2009. http://scholarscompass.vcu.edu/etd/2016.
Full textDuca, Edward. "Invadolysin, a conserved lipid droplet-associated protease interacts with mitochondrial ATP synthase and regulates mitochondrial metabolism in Drosophila." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5562.
Full textHeyno, Eiri. "Production of reactive oxygen species in plasma membranes, mitochondria and chloroplasts." Paris 11, 2009. http://www.theses.fr/2009PA112192.
Full textProduction of reactive oxygen species (ROS) was studied in different subcellular compartments using spectroscopic methods (UV/VIS, fluorescence, infrared and electron paramagnetic resonance). The identities and catalytic mechanisms of ROS-producing enzymes in the plasma membrane (PM) were studied as well as mitochondrial ROS accumulation in response to cadmium (Cd2+) and the protectrice role of the plastid terminal oxidase (PTOX). Cd2+ was shown to be an inhibitor of the PM superoxide (O2. -) –producing NADPH oxidase in vitro. In vivo Cd2+ inhibited the extracellular production of O2. - but stimulated the accumulation of hydrogen peroxide (H2O2 ). Cd2+ induced ROS production in isolated mitochondria. Mitochondrial ROS- inducing inhibitors increased extracellular H2O2 production confirming these organelles the main source of Cd2+ induced extracellular H2O2 generation in vivo. A ROS-producing quinone reductase(QR) was isolated from PMs. ROS production occurred via the pH –dependent deprotonation of the end product menadiol leading to its intermediate forms that react with O2 forming O2. - and H2O2. A potential naphthoquinose species in PMs was identified that could serve as a QR substrate in vivo. The protection of the photosynthetic electron transfer chain by the PTOX, a plastoquinol : O2 oxidoreductase, was studied in PTOX-overexpressing plants (PTOX+ ). Based on the altered response to low and high light conditions in PTOX+ it was proposed that PTOX is coupled to an SOD in order to function as a protective enzyme. The absence of additional chloroplastic SOD in PTOX+ lines might have limited the plant’s ability to detoxify O2. - produced by elevated levels of PTOX+
Kramer, Adam Hildyard. "An investigation of the role of mitochondrial STAT3 and modulation of Reactive Oxygen Species in adipocyte differentiation." Thesis, Rhodes University, 2014. http://hdl.handle.net/10962/54632.
Full textCosta, Rute Alves Pereira e. 1984. "Avaliação das funções mitocondriais de células deficientes na proteína XPC, envolvida na via de reparo por excisão de nucleotídeos (NER) = Evaluation of mitochondrial functions of XPC protein deficient cells, involved in nucleotide excision repair (NER) pathway." [s.n.], 2013. http://repositorio.unicamp.br/jspui/handle/REPOSIP/311361.
Full textTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Xeroderma Pigmentosum (XP) é uma doença rara, autossômica recessiva, caracterizada por fotossensibilidade, mudanças pigmentares, envelhecimento precoce da pele e incidência elevada de neoplasias de pele. XP é causada por mutações em, pelo menos oito genes, que caracterizam sete diferentes grupos de complementação genética (XP-A a XP-G) e um tipo variante (XP-V). Mutações em cada em dos genes envolvidos resultam em diferentes graus de severidade da doença, principalmente quanto ao comprometimento neurológico. Pacientes XP-C apresentam mutações no gene Xpc, que resultam, geralmente, em proteínas truncadas e instáveis. XPC é uma proteína envolvida na via de reparo de DNA por excisão de nucleotídeos (NER) e sua função é reconhecer a lesão na fita de DNA e dar início ao reparo. Recentemente, a participação indireta de XPC no reparo por excisão de bases (BER) foi sugerida, através de sua interação física e funcional com a DNA glicosilase OGG1. Uma vez que OGG1 é essencial para a remoção de purinas oxidadas do DNA mitocondrial, nós hipotetizamos que o DNAmt, e consequentemente a função mitocondrial, estariam comprometidas em células deficientes em XPC. Desta forma, este trabalho se propôs a investigar alterações bioenergéticas mitocondrias em células obtidas de pacientes XP-C. Nossos resultados revelaram que linhagens celulares XP-C apresentavam menor função mitocondrial, apesar de não apresentarem alterações no número de cópias de DNAmt. O consumo de oxigênio pelo complexo I estava significativamente diminuído em células XP-C quando comparado à células controle, enquanto que o consumo de O2 via os complexos II, III e IV foi maior em células XP-C. A capacidade de captar cálcio também se mostrou alterada nas células XP-C, uma vez que essa célula era incapaz de captar e reter concentrações fisiológicas desse íon. A produção de espécies reativas de oxigênio foi significativamente maior em células XP-C comparadas a células controle. Em acordo, a atividade das enzimas antioxidantes superóxido dismutase e glutationa peroxidase foi menor em células XP-C, indicando um desbalanço redox nessas células. A análise da expressão de genes relacionados à biogênese mitocondrial revelou que um regulador transcricional fundamental, o coativador PGC1?, estava significativamente reduzido em células XP-C transformadas e primárias. Resultados de Western blotting e imunofluorescência revelaram que as alterações bioenergéticas e genômicas observadas em células XP-C eram via sinalização e não por efeito direto, uma vez que nas condições experimentais utilizadas neste trabalho, XPC não está presente na mitocôndria. Nossos resultados demonstram, pela primeira vez, que a proteína XPC exerce um papel indireto na manutenção da integridade funcional da mitocôndria, provavelmente através de seu papel no controle da expressão de genes envolvidos na biogênese mitocondrial
Abstract: Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by photosensitivity, pigmentary changes, premature skin aging and increased incidence of skin cancer. XP is caused by mutations in at least eight genes, which characterize seven different genetic complementation groups (XP-A to XP-G) and variant type (XP-V). Mutations in each gene result in varying degrees of severity, mostly regarding the presence or not of neurodegeneration. XP-C is caused by mutations in the Xpc gene, resulting, mostly, in a truncated and unstable protein. The XPC protein is involved in the nucleotide excision repair pathway (NER), where it functions as a damage recognition factor. Recently, a role for XPC in the base excision repair (BER) pathway has been proposed, through its physical and fucntional interaction with the DNA glycosylase OGG1. Since OGG1 has a major function in repairing oxidized purines in the mitochondrial DNA (mtDNA), we hypothesized that XPC played a role in maitaining mtDNA integrity, and consequently, mitochondrial function. Thus, this study proposes to investigate mitocondrial function in XP-C cell. Our results showed that XP-C cells had less mitochondrial function, although without changes in mtDNA copy number. Oxygen consumption through complex I was lower in XP-C cells compared to control cells, while respiration through complexes II, III and IV was higher in XP-C cells. Calcium uptake and retention by mitochondria was also decreased in XP-C cells, as these cells were unable to retain even physiological spikes in calcium concentration. Reactive oxygen species production was significantly higher in XPC cells compared to controls. In agreement to that, the activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase was significatly decreased in XP-C cells, indicating that these cells are under a severe redox signaling inbalance. The analysis of the expression of genes related to mitochondrial biogenesis revealed that the key transcriptional regulator PGC1? was significantly lower in both transformed and primary XP-C cells. The results of Western blotting and imunofluorescence revealed that the bioenergetic impairment observed in XP-C cells is likely the result of changes in expression and signaling pathwyas, since, under the experimental conditions used here, XPC is not present in mitochondria. Our results indicate, for the first time, that XPC plays an important role in mitochondrial maintenace, likely via its role in transcription regulation of mitochondrial biogenesis
Doutorado
Fisiopatologia Médica
Doutora em Ciências
Ho, Hsiang-Ting. "The Role of Reactive Oxygen Species in Arrhythmogenicity of Cardiac Glycoside." The Ohio State University, 2013. http://rave.ohiolink.edu/etdc/view?acc_num=osu1373401702.
Full textSilva, José Pablo. "The pathophysiology of respiratory chain dysfunction /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-234-9/.
Full textBlein, Sophie. "Étude de la variabilité du génome mitochondrial comme facteur de susceptibilité au cancer du sein." Thesis, Lyon 1, 2014. http://www.theses.fr/2014LYO10240/document.
Full textA large part of the genetic component of breast cancer risk (BCR) is still unexplained. Therefore I studied if variants of the mitochondrial genome (mtDNA) might explain a part of this risk. In fact, mitochondria is the main source of reactive oxygen species (ROS), which contribute to genomic instability and tumor development. As a first axis of research, I studied potential interactions between some nuclear and mitochondrial variants, in conjugation to alcohol consumption. Despite the large dimensions of our dataset, the lack of statistical significant interaction in our data might reveal that former published results that show such interactions were not robust. I also studied if mitochondrial haplogroups could be considered as modificators of known association between BCR and pathogenic mutations in the BRCA1/2 genes. I identified haplogroup T1a1 such as modificator for individuals carrying a mutated BRCA2. Finally, I characterized by NGS mitochondrial genome of women diagnosed for a familial breast cancer, but tested negative for known pathogenic BRCA1/2 mutations. Several variants were identified as potentially damaging. Two genes, MT-ATP6 and MT-CYB are specifically enriched both in terms of distinct variants and in the number of individuals carrying these variants. They are both essential structural components of the mitochondrial respiratory chain, the main ROS production source in the cell. All these analyses contribute to enrich the knowledge about associations between BCR and variability of mtDNA, by integrating questions linked to interactions between genomic variants, environmental exposure, and effect modifications related to mitochondrial haplogroups
Zuo, Li. "Molecular Mechanisms of Stress-induced Reactive Oxygen Species Formation in Skeletal Muscle." The Ohio State University, 2002. http://rave.ohiolink.edu/etdc/view?acc_num=osu1038853894.
Full textLucas, Stephen Marc. "Valproic Acid Leads to an Increase in ROS Generation by Inhibiting the Deacetylation of Mitochondrial SOD." BYU ScholarsArchive, 2020. https://scholarsarchive.byu.edu/etd/9247.
Full textBowling, Benjamin D. "Inhibition of mitochondrial protein translation sensitizes melanoma cells to arsenic trioxide cytotoxicity via a reactive oxygen species dependent mechanism." [New Haven, Conn. : s.n.], 2008. http://ymtdl.med.yale.edu/theses/available/etd-11212008-111938/.
Full textBarlow, Jonathan. "Mitochondrial involvement in pancreatic beta cell glucolipotoxicity." Thesis, University of Plymouth, 2015. http://hdl.handle.net/10026.1/3314.
Full textJulienne, Cloé Mimsy. "Altérations du métabolisme énergétique mitochondrial lors de la cachexie cancéreuse." Thesis, Tours, 2012. http://www.theses.fr/2012TOUR3318/document.
Full textCancer cachexia is a composite syndrome, characterized by a negative energetic balance. The role played by mitochondrial energetic metabolism in this syndrome is poor known. Our past work showed a decrease of ATP synthesis efficiency in hepatic mitochondria in severe state of cancer cachexia. In this work, we demonstrate, in vitro, that increase of reactive oxygen species and cardiolipine content, in healthy mitochondria, can partly mimic the mechanisms observed in severe state of cancer cachexia. We observe that alteration of hepatic mitochondrial metabolism appear last during the development of cancer cachexia. In sever state of cancer cachexia, skeletal muscle mitochondria don’t develop this alteration but demonstrated a decrease of oxidative capacities
Lashin, Ossama M. "Functional modification of cardiac mitochondria in type-I diabetes." Connect to text online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1093467515.
Full text[School of Medicine] Department of Physiology and Biophysics. Includes bibliographical references. Available online via OhioLINK's ETD Center.
Barnes, Robert. "A nuclear role for the respiratory enzyme CLK-1 in regulating reactive oxygen species, the mitochondrial unfolded protein response and longevity." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/a-nuclear-role-for-the-respiratory-enzyme-clk1-in-regulating-reactive-oxygen-species-the-mitochondrial-unfolded-protein-response-and-longevity(9a41f8d6-d11d-4102-b250-7b20091f4ded).html.
Full textMacLellan, James Darcy. "Effects of the mitochondrial uncoupling protein 3 on fuel substrate oxidation and reactive oxygen species formation in rat L6 muscle cells." Thesis, University of Ottawa (Canada), 2007. http://hdl.handle.net/10393/27533.
Full textEndoh, Yasumi Medical Sciences Faculty of Medicine UNSW. "New mechanisms modulating S100A8 gene expression." Publisher:University of New South Wales. Medical Sciences, 2008. http://handle.unsw.edu.au/1959.4/42942.
Full textHerb, Marc [Verfasser], Björn [Gutachter] Schumacher, and Martin [Gutachter] Krönke. "Mitochondrial reactive oxygen species license pro-inflammatory signaling in infected macrophages via disulfide linkage of NEMO / Marc Herb ; Gutachter: Björn Schumacher, Martin Krönke." Köln : Universitäts- und Stadtbibliothek Köln, 2019. http://d-nb.info/1178671852/34.
Full textJang, Kyoung-Jin. "Mitochondrial function provides instructive signals for activation-induced B cell fates." Kyoto University, 2015. http://hdl.handle.net/2433/199208.
Full textMerabet, Nadège. "Modélisation mathématique de la production d'espèces actives de l'oxygène par la chaîne respiratoire mitochondriale : vers une meilleure compréhension de l'atrophie optique dominante de type 1." Thesis, Toulouse 3, 2019. http://www.theses.fr/2019TOU30026.
Full textMitochondria are cellular organelles involved in ATP (adenosine triphosphate) supply to cells. Mitochondrial ATP is produced by the oxidative phosphorylation which involves redox reactions catalysed by the four protein complexes of the mitochondrial respiratory chain. These redox reactions require intra-protein electron transfers. The complex I and complex III of the respiratory chain are able to generate superoxide anion, which is formed by the reaction of oxygen with one electron. Reactive oxygen species (ROS) are molecules derived from the superoxide anion. ROS which are not regulated by cellular antioxidant defences can react with the components of the cells and disturb its functioning: this imbalance between ROS and antioxidant defences has been termed “oxidative stress”. Dysfunctions of one or several respiratory complexes associated to an oxidative stress is a mechanism common to numerous neurodegenerative diseases. In this work, we focus on autosomal dominant optic atrophy 1 (ADOA-1 or DOA-1). DOA-1 is a neurodegenerative pathology mainly caused by mutations in the gene OPA1 which codes for a mitochondrial protein involved in mitochondrial dynamics. The symptoms and ages of onset of the disease are variable. There is no clear correlation between genotypes and phenotypes which can explain this variability and to date, there is no established medical treatment for the disease. The hypothesis of an oxidative stress has been proposed to explain the variability of symptoms observed in patients. Indeed, the mitochondrial energetic metabolism is altered in biological models (cell cultures and animal models) of DOA-1 and low levels of antioxidant defences have been measured in cells from patients suffering from severe forms of the pathology. Hence, our objective is to improve the understanding of the physio-pathological mechanisms involved in this disease by developing mathematical models of ROS production by the respiratory chain. We use two modelling methods. The first method consists in modelling the activities of respiratory complexes and the superoxide production by complexes I and III with rate equations that we build in three steps. We first analyse the biochemical data available in the literature. We subsequently interpret this data physically and translate them in the form of fuzzy rules. We then model these rules with mathematical functions provided by the formalism of Michaelis-Menten. The rate equations depend on chemical variables such as the concentrations of chemical species involved in the reactions catalysed by the respiratory complexes. They do not include the details of intra-protein electron transfers, occurring during the catalysis performed by the complexes. This method enables us to build a simple model simulating the activities and superoxyde productions of complexes I and III in different conditions and that can easily be modified or integrated in a more comprehensive model of the mitochondrion. Our model of complex I can simulate the forward and reverse activities and ROS productions of the enzyme for different concentrations of substrates and products
Belikov, Aleksey Vitalyevich [Verfasser], and Luca [Akademischer Betreuer] Simeoni. "The role of reactive oxygen species and mitochondria in T-cell activation / Aleksey Vitalyevich Belikov. Betreuer: Luca Simeoni." Magdeburg : Universitätsbibliothek, 2016. http://d-nb.info/1100055479/34.
Full textDesmoulins, Lucie. "Détection hypothalamique du glucose chez le rat soumis à un régime gras enrichi en saccharose : rôle de la dynamique mitochondriale et des espèces actives de l'oxygène d'origine mitochondriale." Thesis, Dijon, 2016. http://www.theses.fr/2016DIJOS024/document.
Full textThe hypothalamus participates in the control of energy homeostasis by detecting circulating nutrients, such as glucose. The mediobasal hypothalamus (MBH), in particular, senses hyperglycemia and initiates physiological responses, e.g., insulin secretion via the autonomous (vagal) nervous system. We have recently demonstrated that glucose sensing requires mitochondrial reactive oxygen species (mROS) signaling heavily dependant on mitochondrial fusion and fission (dynamics). Recently, genetic models have associated some of these dynamics within the MBH to their obesogenic susceptibility. The aims of my thesis were first to establish a model that only presents a hypothalamic glucose sensing defect induced by a high fat high sucrose (HFHS) feeding in rats. After caracterizing this model, our objectives were to determine whether modulating the diet affects mitochondrial dynamics, and thus, mROS signaling, through the mitochondrial respiratory function in the hypothalamus. We finally reversed some dysregulated metabolic signalings potentially involved in mitochondrial dynamics in order to reverse the phenotype observed in HFHS fed rats. Our results demonstrate that after 3 weeks of HFHS feeding, rats had a normal body weight despite an increase in the fat mass compared to control rats. HFHS fed rats displayed also a glucose intolerance, increased fasting glycemia but no modification of fasting insulinemia. Hypothalamic glucose sensing induced insulin secretion, measured after an intra-carotid glucose injection towards the brain that only increases brain glycemia without alteration in peripheral glycemia, was drastically decreased. However, glucose stimulated insulin secretion in isolated islets was not different compared to controls. These defects correlate with a decrease of MBH ROS production in response to glucose, with no modification in the redox status. Efficiency of hypothalamic mitochondrial respiration was evaluated using oxygraphy, and results showed mitochondrial respiratory deficiencies in HFHS fed rats. The fission protein DRP1 exhibited decreased mitochondrial translocation in the MBH in response to glucose, suggesting decreased mitochondrial fission. The increase of AMPK activation in the hypothalamus was not responsible for the alteration of hypothalamic glucose sensing since its reversal with an intracerebroventricular (ICV) injection of compound C failed to restore brain hyperglycemia induced insulin secretion. Likewise, an ICV injection of leptin that induced STAT3 activation also failed to restore brain hyperglycemia induced insulin secretion. Finally, the decrease in AKT activation suggested a central insulin resistance. These results demonstrate for the first time that hypothalamic alteration of mitochondrial ROS signaling, fission and respiration were present in rats exposed to a 3 weeks HFHS diet. Such hypothalamic glucose sensing defects are early events preceding those in islets. These early but drastic hypothalamic modifications could participate in a primary nervous defect of the control of insulin secretion, and finally, the etablishment of a diabetic phenotype
Aitken, Gillian Roxburgh. "Investigation of UV-induced reactive oxygen and nitrogen species in human skin cells and its association with the individual complexes of the mitochondrial electron transport chain." Thesis, University of Newcastle Upon Tyne, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424156.
Full textBagsiyao, Pamela. "Role of brain uncoupling proteins in energy homostasis and oxygen radical metabolism." Honors in the Major Thesis, University of Central Florida, 2007. http://digital.library.ucf.edu/cdm/ref/collection/ETH/id/1025.
Full textBachelors
Burnett College of Biomedical Sciences
Molecular Biology and Microbiology
Dehina, Leila. "Influence de l’ischémie et de la cinétique de reperfusion myocardique sur la structure et le fonctionnement des mitochondries chez le porc : effets de la trimétazidine, de la ranolazine et du propranolol." Thesis, Lyon 1, 2013. http://www.theses.fr/2013LYO10006.
Full textThe generation of reactive oxygen species (ROS), the cytosolic calcium overload and the opening of mitochondrial permeability transition pores (mPTP) resulting from myocardial ischemia (MI) are aggravated during reperfusion. In the present work, the following points have been addressed: 1) the evaluation of trimetazidine effects on the electrical threshold of ventricular fibrillation (VFT) and both structural and functional alterations of mitochondria during MI (study 1, N=26 pigs); 2) the determination of the kinetics of ischemia/reperfusion (I/R) lesions (study 2a, N=30 pigs); 3) the protective effects of ranolazine and propranolol, alone or combined on I/R lesions (study 2b, N=30 pigs). All studies were performed in anesthetized pigs. They allowed to follow changes in cardiac electrophysiological and hemodynamic parameters and, at the cellular level, changes in the structure and function of mitochondria. The obtained results show: 1) in study 1, that TMZ can prevent the drop in VFT and all structural and functional alterations of mitochondria noticed during MI; 2) in study 2a, that the lesions seen during MI are significantly aggravated within the first seconds of reperfusion whereas some improvement is observed after 10 minutes and more markedly after 45 minutes of reperfusion; 3) in study 2b, that pretreatment with ranolazine or propranolol, alone or combined can reduce the severity of I/R lesions. The molecular and cellular mechanisms of action of both agents are thought to be involved in this improvement of I/R lesions
Pan, Minglin, Ying Han, Rui Si, Rui Guo, Ankit Desai, and Ayako Makino. "Hypoxia-induced pulmonary hypertension in type 2 diabetic mice." SAGE PUBLICATIONS INC, 2017. http://hdl.handle.net/10150/623894.
Full textSavu, Octavian. "Mechanisms of chronic complications of diabetes with focus on mitochondria and oxygen sensing." Stockholm, 2010. http://diss.kib.ki.se/2010/978-91-7409-764-1/.
Full textGiedt, Randy James. "Real-Time Acquisition and Analysis of Endothelial Mitochondrial Superoxide Radical Production and Membrane Potential During In Vitro Ischemia/Reperfusion." The Ohio State University, 2009. http://rave.ohiolink.edu/etdc/view?acc_num=osu1243541457.
Full textGiedt, Randy James. "Mitochondrial Network Dynamics in Vascular Endothelial Cells Exposed to Mechanochemical Stimuli: Experimental and Mathematical Analysis." The Ohio State University, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=osu1333985787.
Full textSemont, Audrey. "Implication des ROS mitochondriaux dans le couplage excitation contraction cardiaque." Thesis, Bordeaux, 2019. http://www.theses.fr/2019BORD0426.
Full textThe electrical activation of the cardiomyocyte through a generated depolarisation current is essential in the cardiac contraction, which requires the adequacy of the mitochondrial energy production and the energy needs of the contractile system. Radical oxygen species (ROS) have recently been involved in the regulation of many actors of the excitation-contraction coupling. The aim of this study was to explore the involvement of mitochondrial ROS in the regulation of the excitation-contraction coupling in cardiomyocytes, under physiological and pathological conditions. A model of endogenous ROS overproduction with the use of succinate was developed in isolated rat cardiomyocytes. Different pharmacological protocols, using various antioxidants (Trolox, Mito-Tempo,EUK and OP2113) allowed us to establish the mitochondrial origin of ROS production. Finally, the use of OP2113, (a specific inhibitor of mitochondrial ROS production, Patent P.Diolez) enabled us to establish that approximately 80 % of ROS production came from complex I in the respiratory chain. To start with, isolated cardiomyocytes were used to study the effects of mitochondrial ROS on different excitation-contraction coupling parameters. Succinate induced an overproduction of mitochondrial ROS, which lead to a drop of 50% of the contraction amplitude. The initial amplitude of contraction wasrecovered with addition of Trolox, Mito Tempo or OP2113, which demonstrates the implication of mitochondrial ROS produced at the site of Iq. Secondly, the overproduction of ROS leadsto a decrease of the calcium transient amplitude, due to a decrease of systolic calcium concentration during contraction. These effects were inhibited by Trolox and OP2113. Finally, mitochondrial calcium concentration was modulated with the use of Cyclosporin A (mitochondrial transition pore inhibitor) and Ru360 (mitochondrial calcium entry inhibitor). The inhibitors induced a ROS production unresponsive to Trolox and OP2113. The origin of which remains to be established. To conclude, an increase of mitochondrial ROS production results in a decrease of contraction amplitude and calcium transients. Our overall results demonstrate the critical significance of the mitochondrion in the excitation-contraction coupling. Our results open new therapeutic perspectives in the context of acute or chronic heart failure
Assaly, Rana. "Protection du myocarde ischémique et pore géant mitochondrial : applications pharmacologiques." Phd thesis, Université Paris Sud - Paris XI, 2011. http://tel.archives-ouvertes.fr/tel-00734466.
Full textSilva, Carolina Solon da 1982. "Apoptose induzida por palmitato em células HEPG2 depende da produção de TNF-Alfa." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/309382.
Full textDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A prevalência de esteato hepatite não alcólica (NASH) aumenta de 20% em indivíduos magros para 80% em pacientes obesos com inflamação hepática caracterizada por elevados níveis de TNF-alfa. Um dos eventos que caracteriza a evolução para NASH é a marcante morte de hepatóciotos resultante da ação do excesso de ácidos graxos livres circulantes. O mecanismo pelo qual o palmitato induz a apoptose é dependente, entre outros parâmetros, do aumento dos níveis de espécies reativas de oxigenio (EROS). O objetivo do presente trabalho foi avaliar se a apoptose de hepatócitos induzida pelo palmitato é dependente do aumento da produção de TNF-alfa. Para testar tal hipótese, utilizamos o Infliximabe, um anticorpo monoclonal específico anti-TNF-alfa, como ferramenta farmacológica para reverter as injúrias provocadas pelo palmitato. Foi observado que após 6 horas de tratamento com o palmitato houve um aumento de expressão de mRNA de TNF-alfa levando a um aumento de apoptose 24 horas após à exposição com o ácido graxo. Este fenômeno concordou temporalmente com um aumento na fosforilação das proteínas IkK, IKbeta e JNK, indicativo de ativação da via de sinalização do TNF-alfa. A apoptose induzida pelo palmitato foi revertida pela adição de um inibidor geral de síntese proteica (Ciclohexamida) ou de um anticorpo neutralizante para o TNF-alfa circulante. Além disso, a produção de EROs e a disfunção mitocondrial induzidas pelo palmitato também foram revertidos por estas estratégias farmacológicas. Com base em tais resultados, concluímos que a apoptose, o acúmulo de EROs e da disfunção mitocondrial induzidas pelo palmitato em células HepG2 são dependentes da produção de TNF-alfa
Abstract: In the last three decades, the prevalence of overweight and obesity has been continuously increasing. Obesity is a risk factor for developing a series of diseases such as whole-body insulin resistance and type 2 diabetes mellitus. Adipose tissue, originally considered merely energy storage, today is recognized as an endocrine organ able of secreting a variety of cytokines, hormones and other substances with specific biological activities, such as saturated fatty acids. Both long chain saturated fatty acids, like palmitate, and the proinflammatory cytokines, as TNF-alfa, are known to activate signaling pathways that promote apoptosis. The mechanism by which the palmitate induces apoptosis is dependent on cell type, for example, human hepatocellular carcinoma line (HepG2) treated with palmitate led lipotoxicity and to increased levels of reactive oxygen species (ROS). Thus, the objective of this study was to evaluate whether apoptosis in HepG2 cells is dependent on increased production of TNF-alfa induced by treatment with palmitate. To test this hypothesis, we used the Infliximab, a monoclonal antibody anti-TNF-alfa, as a pharmacological tool to reverse injuries caused by palmitate. We observed that palmitate increased the mRNA for TNF-alfa and phosphorylation of IkK, Ikbeta and JNK, all indicative of activation of inflammatory signaling pathways. Apoptosis induced by palmitate was suppressed by simultaneous treatment with cycloheximide or infliximab. Furthermore, the production of ROS and mitochondrial dysfunction induced by palmitate were also suppressed by these two pharmacological strategies. Based on these results, we conclude that apoptosis and related events such as increased ROS production and mitochondrial dysfunction induced by palmitate in HepG2 cells are dependent on autocrine action of TNF--alfa
Mestrado
Farmacologia
Mestra em Farmacologia
Semete, Boitumelo. "Analysis of metallothionein gene expression in oxidative stress related disorders / by Boitumelo Semete." Thesis, North-West University, 2004. http://hdl.handle.net/10394/51.
Full textThesis (Ph.D. (Biochemistry))--North-West University, Potchefstroom Campus, 2005.