To see the other types of publications on this topic, follow the link: Superoxide dismutase.
Dissertations / Theses on the topic 'Superoxide dismutase'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 dissertations / theses for your research on the topic 'Superoxide dismutase.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse dissertations / theses on a wide variety of disciplines and organise your bibliography correctly.
1
Dufernez, Fabienne. "Les superoxyde dismutases des protistes : caractérisation et origine phylogénétique." Lille 2, 2005. http://www.theses.fr/2005LIL2S030.
Full textAbstract:
Les organismes aérobies ont développé des mécanismes pour se protéger des attaques des espèces activées de l'oxygène produites lors du métabolisme cellulaire. La superoxyde dismutase (SOD) est une métalloenzyme du système de défense anti-oxydant. Elle catalyse la dismutation de l'anion superoxyde en peroxyde d'hydrogène. Les SOD se divisent en 2 grandes familles qui diffèrent fondamentalement d'un point de vue structural : les SOD qui utilisent simultanément le cuivre et le zinc comme métaux cofacteurs (Cu/Zn-SOD) et les SOD utilisant soit le fer (FeSOD) soit le manganèse (MnSOD) comme métal cofacteur. Sur la base d'un alignement de 261 séquences de SOD et de 12 structures cristallographiques de SOD à fer et à manganèse, nous avons analysé les conservations en terme de structure et de séquence parmi les SOD à fer et à manganèse. Les résidus caractéristiques de la fonction enzymatique, de la conformation en dimère ou tétramère et de la spécificité de métal ont été identifiés. Toutes ces données nous ont été utiles lors de nos études de SOD de nombreux protozoaires. Les protozoaires parasites étudiés jusqu'à présent ont ,en effet, la particularité de ne contenir qu'un seul type de SOD, des FeSOD qui différent des Cu/Zn SOD et SOD tétramérique à manganèse présentes chez l'humain. Ceci fait de la SOD à fer des protistes une cible thérapeutique potentielle. Chez Trypanosoma brucei, agent de la maladie du sommeil, nous avons identifié 4 gènes de SOD après interrogation des banques de données du programme de séquençage : soda, sodb1 et sodb2 ainsi que sodc nouvellement identifié. Ces 4 gènes correspondaient à des SOD dimériques à fer. Les protéines recombinantes correspondantes ont été produites et se sont révélées actives. Des modélisations structurales ont été réalisées par homologie avec des structures cristallographiques connues et ont montrées une grande similarité de structure entre ces FeSOD. Afin de déterminer la localisation cellulaire, nous avons réalisé des expériences de fusion de chacune de ces enzymes avec la GFP, ces constructions ont été transfectées dans des cellules procycliques de trypanosome. Nous avons alors mis en évidence la localisation mitochondriale des 2 enzymes FeSODA et FeSODC et la présence des FeSODB dans le cytoplasme et les glycosomes, localisation confirmée par un marquage sur fractions cellulaires : la FeSODB1 étant plutôt cytosolique et la FeSODB2 plutôt glycosomale. Chez le dinoflagellé Crypthecodinium cohnii nous n'avons retrouvé que des activités SOD correspondantes à des SOD à fer. Une famille multigénique codant pour des FeSOD a été caractérisée. La protéine recombinante correspondante à un gène complet de FeSOD dimérique a été produite et s'est révelée active. Les SOD d'un second prostiste parasite Trichomonas vaginalis ont également été étudiées. T. Vaginalis est responsable de la trichomoniase humaine, la maladie sexuellement transmissible la plus répandue à travers le monde. La recherche dans les bases de données du programme de séquençage du parasite nous a permis d'identifier 7 gènes de SOD chez ce parasite. Ces SOD comportent toutes les caractéristiques des SOD à fer dimériques et sont actives lorsqu'on les produit sous forme de protéines recombinantes. La protéine recombinante SOD6 de T. Vaginalis a été également purifiée et la structure cristallographique obtenue. Ces données sont essentielles pour la conception éventuelle d'inhibiteurs. Toutes ces séquences de FeSOD ont été incluses dans une large analyse phylogénétique afin de proposer une origine pour les FeSOD des protistes. Cette analyse confirme l'origine bactérienne de ces enzymes via des transferts de gènes de bactéries vers les protistes, suivi de duplications successives.
2
Olofsson, Eva. "Superoxide dismutase 1 and cataract." Doctoral thesis, Umeå : Umeå universitet, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-21032.
Full text
3
Kolahi-Ahari, Ali. "A study of superoxide dismutase activity and superoxide production in kiwifruit." Thesis, University of Canterbury. Biological Sciences, 2006. http://hdl.handle.net/10092/1343.
Full textAbstract:
The activity of superoxide dismutase (SOD) was determined in three kiwifruit (Actinidia) species including A. deliciosa, A. chinensis, and A. arguta. Among the species tested, the highest SOD activity was found in crude extracts prepared from fruit tissues of A. deliciosa. The highest enzyme activity was localized in seed, followed by locules, core and outer pericarp (OP). SOD activity in crude extract of whole fruit remained stable for at least one month when stored at -20℃. The effect of synthetic protease inhibitors (PI) on SOD activity was investigated. Supplementing crude kiwifruit extracts with PI improved SOD activity in freshly prepared extracts, and in extracts stored at 4℃, but had no effect on those stored at -20℃. Among the PI used, iodoacetamide (an inhibitor of cysteine proteases, for example, actinidin which is a principal protease found in kiwifruit) and PMSF (an inhibitor of serine proteases), had the most and least influence on SOD activity in crude kiwifruit extracts, respectively. There was a significant increase in SOD activity in kiwifruit (that were relatively firm) when the fruits were stored at low temperature (4℃). An increase in SOD activity was also correlated with a decrease in fruit firmness. Staining fruit tissues with nitroblue tetrazolium (NBT) provided evidence for stress-induced superoxide generation in kiwifruit tissues. Taken together, the changes in SOD activity and the capacity for stress-inducible superoxide production in post-harvest kiwifruit suggest that SOD might play a fundamental role in the storage life/ripening of kiwifruit.
4
Parker, Michael William. "Structural studies on manganese superoxide dismutase." Thesis, University of Oxford, 1985. https://ora.ox.ac.uk/objects/uuid:b8fff51f-1e2f-41b1-baff-4e95b499f0de.
Full textAbstract:
Superoxide dismutases are widely distributed enzymes which catalyse the dismutation of superoxide radicals to dioxygen and hydrogen peroxide and are considered to be an important agent of an organism's defence against oxygen toxicity. The crystallization and low resolution structure determination of manganese superoxide dismutase (E.G. 1.15.1.1) from Bacillus stearothermophiluB is described. The enzyme crystallized in space group P21212 with two monomers per asymmetric unit and cell dimensions of ̲a=72.2Ã
, ̲b=111.1Ã
and ̲c=51.1Ã
. The crystals diffracted to beyond 2Ã
resolution but were fragile and prone to cell dimension changes. The cell dimension variability was overcome to some extent by crossllnking with glutaraldehyde. An electron density map was calculated to 6Ã
resolution initially by the method of multiple isomorphous replacement using data obtained from six heavy atom derivatives. The final map was calculated from single isomorphous replacement data using a map modification procedure. The fitting of an alpha carbon model of iron superoxide dismutase into the map suggested the iron and manganese enzymes are structurally related. The position of the metal atoms in the model solved difference Patterson maps calculated from data collected from a manganese-free crystal and from anomalous dispersion data. The latter data were collected using synchrotron radiation tuned close to the manganese absorption edge. The low resolution map and the availability of 2.4Ã
resolution native data paves the way for higher resolution X-ray studies of the crystals. A detailed analysis of amino acid sequences has been carried out on the various metal-containing superoxide dismutases. The results indicate that the enzymes can be classified according to their metal cofactor. The distribution and homology of the enzyme classes supports the endosymbiotic theory of the origin of cell organelles. The presence of the copper/zinc enzyme in Photobacterium leiognathi is shown to support the case for a eukaryote to prokaryote gene transfer.
5
Barkley, Katherine Byer. "Characterization of superoxide dismutase from Actinomyces." Diss., Virginia Polytechnic Institute and State University, 1988. http://hdl.handle.net/10919/53905.
Full textAbstract:
The anaerobes Actinomyces naeslundii, A. odontolyticus and Actinomyces strain ii E1S.25D produce a Mn-containing superoxide dismutase (MnSOD). Actinomyces, once classified as yeast based on their morphology, are saprophytic organisms found among the normal flora of the mouth but can act as endogenous pathogens resulting in gingivitis and actinomycosis. The ability of Actinomyces to scavenge superoxide may increase survival of the cell from the O₂⁻-dependent killing by polymorphonuclear leukocytes and also enable the organism to be transported through an oxygenated environment from one site to another. The MnSODs were purified 85-240 fold from crude extracts with 30-60% yield by two chemical fractionations and three chromatography steps. The enzymes, Mr 96,000, were tetramers of equally sized, noncovalently associated subunits similar to the MnSOD found in Saccharomyces cerevisiae. Each of the Actinomyces MnSODs contained 0.5 g-atoms Mn/subunit and were stable in the presence of 1 mM NaCN, 1 mM NaN₃ and 2.5 mM H₂O₂. The MnSODs from Actinomyces have isoelectric points of 4.2-4.6 and are negatively charged at physiological pH. Amino acid analyses of the high molecular weight MnSODs from Actinomyces, yeast, chicken liver, and Thermus thermophilus indicated similar composition of each subunit. The second order rate constants of each Actinomyces MnSOD were measured at pH 7.8 and found to be in the range of 0.9 - 2.8 x 10⁹ M⁻¹ sec⁻¹ as compared to the rate of 1.8 x 10⁹ M⁻¹ sec⁻¹ for yeast MnSODs. Structural relatedness was evaluated by immunological studies. Rabbit antisera to each of the Actinomyces MnSODs were prepared. The MnSODs from A. naeslundii and Actinomyces strain E1S.25D both showed complete identity with their respective antibodies and partial identity with the antibody prepared against A. odontolyticus MnSOD. None of the antisera cross reacted with bovine Cu/Zn SOD, Bacteroides Fe- or MnSOD or MnSODs from either Haemophilus influenzae, Deinococcus radiodurans, or S. cerevisiae.Ph. D.
6
Meissner, Felix. "Superoxide dismutase 1 regulates caspase-1." Berlin mbv, 2008. http://d-nb.info/992999286/04.
Full text
7
Jonsson, P. Andreas. "Superoxide dismutase 1 and amyotrophic lateral sclerosis." Doctoral thesis, Umeå : Medical Biosciences, 2005. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-611.
Full text
8
Enayat, Zinat Ellaheh. "Superoxide dismutase mutations and amyotrophic lateral sclerosis." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.400500.
Full text
9
Blackney, Michael James. "Characterising the Drosophila extracellular superoxide Dismutase gene." Thesis, University of Southampton, 2010. https://eprints.soton.ac.uk/179761/.
Full textAbstract:
The indiscriminate action of reactive oxygen species (ROS), if left unregulated, has long been considered contributory to a range of disease processes within the animal kingdom and is also a factor associated with ageing. Consequently modifying the molecular mechanisms that regulate ROS levels may prove therapeutic and could also positively affect longevity. One of the key components of this machinery is the superoxide dismutase (SOD) family of enzymes which regulate ROS levels by scavenging the ROS superoxide. Mammals have three distinct SOD enzymes each responsible for managing superoxide levels in different cellular compartments. In Drosophila homologues of two of the mammalian SODs, the intracellular (SOD1) and mitochondrial (SOD2) SODs, have been identified and studied extensively demonstrating a clear link between SOD and oxidative protection and survival. Recently the sequence of a third sod gene, homologous to both the relatively poorly characterised mammalian (sod3) and C. elegans (sod-4) extracellular sod, was identified in Drosophila and is also predicted to locate extracellularly (sod3). To date, no (published) work has been carried out to assess the role of sod3 within insects. This thesis reports the molecular and biochemical characteristics of sod3 in Drosophila. Detailed within are the steps taken to clone the sod3 gene which appears to be expressed as two gene products formed by alternative splicing. Furthermore, a combination of gene expression, proteomic and functional analysis of a number of sod mutants was used to: i) reveal sex specific sod gene expression; ii) validate a sod3 hypomorph mutant; iii) indicate a functional role for sod3 in protection against H2O2 induced oxidative stress; iv) suggest a SOD1-SOD3 co-dependency for maintaining Cu Zn SOD activity; v) demonstrate the appearance of genetic modifiers in the sod3 hypomorph. The findings of this report and further studies on the Drosophila sod3 gene should encourage the re-evaluation of the previous work concerning SOD’s influence on disease states and lifespan regulation.
10
Matemadombo, Fungisai. "Metallophthalocyanines as electrocatalysts and superoxide dismutase mimics." Thesis, Rhodes University, 2010. http://hdl.handle.net/10962/d1004985.
Full textAbstract:
Syntheses, spectral, electrochemical, and spectroelectrochemical studies of iron, cobalt, and manganese phthalocyanines are reported. The novel coordination of cobalt tetracarboxy metallophthalocyanine to an electrode premodified with aryl radicals and its use in the detection of thiocyanate are reported. This work describes the catalytic activity of cobalt phthalocyanine (CoPc) derivatives adsorbed onto glassy carbon electrodes for the electrocatalytical detection of nitrite, Lcysteine, and melatonin. The modified electrodes efficiently detected nitrite. The CoPc derivative modified electrodes proficiently detected L-cysteine whereas an un-modified electrode could not. This work presents the innovative electrochemical detection of melatonin using electrodes adsorbed with CoPc derivatives. These electrodes detected melatonin at more favorable electrochemical parameters relative to an un-modified gold electrode. The limits of melatonin detection of the modified electrodes lay in the 10⁻⁷ to 10⁻⁶ M region. The modified electrodes accurately detected capsule melatonin concentrations as specified by the supplier and could differentiate between a mixture of melatonin, tryptophan, and ascorbic acid. They reliably detected nitrite, L-cysteine, and melatonin in the 10⁻⁴ to 10⁻² M region. Metallophthalocyanine complexes substituted with thio groups were employed as self assembled monolayers (SAMs). Voltammetry, impedance, atomic force microscopy, and scanning electrochemical microscopy proved that the SAMs all act as selective and efficient barriers to ion permeability. All the SAMs in this work can be used as effective electrochemical sensors of nitrite and L-cysteine in the 10⁻⁴ to 10⁻² M region with competitive limits of detection whereas an un-modified electrode cannot detect Lcysteine. The manganese phthalocyanine SAM modified electrodes are arguably better nitrite and L-cysteine electrocatalysts relative to their iron and cobalt counterparts. Manganese phthalocyanines were used as superoxide dismutase (SOD) mimics. All manganese phthalocyanine complexes in this work acted as SOD mimics in an enzymatic system of superoxide production. From cellular studies, complexes 6d, 6e, 8d, 8e act as intracellular SOD mimics and are without significantly high cellular toxicity.
11
Zetterström, Per. "Misfolded superoxide dismutase-1 in amyotrophic lateral sclerosis." Doctoral thesis, Umeå universitet, Klinisk kemi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-43898.
Full textAbstract:
Amyotrophic lateral sclerosis (ALS) is a disease in which the motor neurons die in a progressive manner, leading to paralysis and muscle wasting. ALS is always fatal, usually through respiratory failure when the disease reaches muscles needed for breathing. Most cases are sporadic, but approximately 5–10% are familial. The first gene to be linked to familial ALS encodes the antioxidant enzyme superoxide dismutase-1 (SOD1). Today, more than 160 different mutations in SOD1 have been found in ALS patients. The mutant SOD1 proteins cause ALS by gain of a toxic property that should be common to all. Aggregates of SOD1 in motor neurons are hallmarks of ALS patients and transgenic models carrying mutant SOD1s, suggesting that misfolding, oligomerization, and aggregation of the protein may be involved in the pathogenesis. SOD1 is normally a very stable enzyme, but the structure has several components that make SOD1 sensitive to misfolding. The aim of the work in this thesis was to study misfolded SOD1 in vivo. Small amounts of soluble misfolded SOD1 were identified as a common denominator in transgenic ALS models expressing widely different forms of mutant SOD1, as well as wild-type SOD1. The highest levels of misfolded SOD1 were found in the vulnerable spinal cord. The amounts of misfolded SOD1 were similar in all the different models and showed a broad correlation with the lifespan of the different mouse strains. The misfolded SOD1 lacked the C57-C146 intrasubunit disulfide bond and the stabilizing zinc and copper ions, and was prinsipally monomeric. Forms with higher apparent molecular weights were also found, some of which might be oligomers. Misfolding-prone monomeric SOD1 appeared to be the principal source of misfolded SOD1 in the CNS. Misfolded SOD1 in the spinal cord was found to interact mainly with chaperones, with Hsc70 being the most important. Only a minor proportion of the Hsc70 was sequestered by SOD1, however, suggesting that chaperone depletion is not involved in ALS. SOD1 is normally found in the cytoplasm but can be secreted. Extracellular mutant SOD1 has been found to be toxic to motor neurons and glial cells. Misfolded SOD1 in the extracellular space could be involved in the spread of the disease between different areas of the CNS and activate glial cells known to be important in ALS. The best way to study the interstitium of the CNS is through the cerebrospinal fluid (CSF), 30% of which is derived from the interstitial fluid. Antibodies specific for misfolded SOD1 were used to probe CSF from ALS patients and controls for misfolded SOD1. We did find misfolded SOD1 in CSF, but at very low levels, and there was no difference between ALS patients and controls. This argues against there being a direct toxic effect of extracellular SOD1 in ALS pathogenesis. In conclusion, soluble misfolded SOD1 is a common denominator for transgenic ALS model mice expressing widely different mutant SOD1 proteins. The misfolded SOD1 is mainly monomeric, but also bound to chaperones, and possibly exists in oligomeric forms also. Misfolded SOD1 in the interstitium might promote spread of aggregation and activate glial cells, but it is too scarce to directly cause cytotoxicity.
12
Quebec, Elizabeth Ann Hayes. "Crosslinked hemoglobin-superoxide dismutase-catalase and methemoglobin formation." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp01/MQ29863.pdf.
Full text
13
Regan, Elizabeth Anne. "Extracellular superoxide dismutase and oxidant stress in osteoarthritis /." Connect to full text via ProQuest. IP filtered, 2006.
Find full textAbstract:
Thesis (Ph.D. in Clinical Science) -- University of Colorado at Denver and Health Sciences Center, 2006.Typescript. Includes bibliographical references (leaves 107-128). Free to UCDHSC affiliates. Online version available via ProQuest Digital Dissertations;
14
Wong, Kwan-yeung. "Roles of manganese superoxide dismutase in ovarian cancer." Click to view the E-thesis via HKUTO, 2007. http://sunzi.lib.hku.hk/hkuto/record/B39364689.
Full text
15
Wong, Kwan-yeung, and 黃君揚. "Roles of manganese superoxide dismutase in ovarian cancer." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39364689.
Full text
16
Temperton, Nigel James. "Functional studies on superoxide dismutase in Trypanosoma cruzi." Thesis, London School of Hygiene and Tropical Medicine (University of London), 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.391814.
Full text
17
Chen, Ying. "In vivo metal substitution in bacteroides superoxide dismutase." Thesis, Virginia Tech, 1989. http://hdl.handle.net/10919/44628.
Full textAbstract:
The effect of various growth conditions on the type of superoxide dismutase (SGD) formed anaerobically in three Bacteriodes species was studied. B. fragilis, B. distasonis, and B. thetaiotaomicron were grown in ironâ restricted media with or without manganese supplementation. Iron availability was decreased by treatment of the media with chelex-100, a metal-chelating resin, and addition of desferrioxamine mesylate (desferal, Ciba-Geigy), an iron chelator. Mn-containing (MnSOD) and Fe-containing superoxide dismutase (EeSOD) activities in cell extracts were differentiated by inhibition with azide and inactivation by H202. The amount of Mn-containing superoxide dismutase was estimated by the fraction of azide- and H202, -resistant activity. Cells grown in untreated media contained approximately 90% FeSOD and 10% MnSOD. Cells grown in Fe-restricted media supplemented with graded amounts of manganese synthesized a progressively larger fraction of MnSOD. Hemin, added to the Fe-restricted media, did not serve as an iron source for FeSOD formation. Superoxide dismutase specific activities varied (3-6 U/mg) in each extract but not as a function of manganese concentration.
Master of Science
18
Mazura, Sergiy. "Effect of active pharmaceutical ingredients on superoxide dismutase." Thesis, Київський національний університет технологій та дизайну, 2019. https://er.knutd.edu.ua/handle/123456789/13082.
Full text
19
Vinatier, Virginie. "Exploration de la voie péroxynitrite : nouveaux donneurs de NO, étude des superoxyde dimutases à fer et application à la conception d’inhibiteurs." Toulouse 3, 2007. http://www.theses.fr/2007TOU30008.
Full textAbstract:
Ce travail aborde divers aspects de la chimie du peroxynitrite et de ses précurseurs , le superoxyde et le monoxyde d’azote. Plusieurs donneurs de NO dérivés du SIN-1 ont été synthétisés et étudiés dans le but de diminuer la quantité de péroxynitrite formé pendant la décomposition et d’augmenter la biodisponibilité du NO. Les superoxyde dismutases à fer, enzymes protégeant les protozoaires du stress oxydant, des parasites Plasmodium falciparum, Trypanosoma cruzi et Trypanosoma brucei ont été surexprimées et caractérisées afin de découvrir de nouveaux composés antiparasitaires. La structure de ces enzymes partiellement inactivées par la nitration du résidu tyrosine 34 a été étudiée et modélisée tandis que plusieurs stratégies ont été utilisées pour la conception d’inhibiteurs. Les modes de liaison de ces composés ont été étudiés par amarrage moléculairePeroxynitrite is the product of the very fast reaction between nitrogen oxide and superoxide. This work tackles several sides of the chemistry of these compounds. Several SIN-1 derivatives with NO releasing properties were synthesised and studied to reduce peroxynitrite production and thus increase the NO availability. Iron Superoxide Dismutases (SOD) are enzymes that protect protozoans from the oxidative stress. Enzymes from parasites Plasmodium falciparum, Trypanosoma cruzi and Trypanosoma brucei were overexpressed and characterised in order to find some new compounds with antiparasitic activity. Iron SODs are partially inactivated by nitration of the residue tyrosine 34 by peroxynitrite. The structure of the nitrated enzyme was studied and modelised. Several methods of “de novo” conception of inhibitors are descried and the binding modes of these compounds were studied by docking experiments
20
Poinso, Alix. "Recherche d'inhibiteurs de la superoxyde dismutase à partir de substances naturelles." Thesis, Toulouse 3, 2016. http://www.theses.fr/2016TOU30378/document.
Full textAbstract:
Le but de ce travail de thèse était de rechercher de nouvelles molécules inhibitrices de la SOD dans des extraits de substances naturelles. Cette enzyme majeure du stress oxydant étant impliquée dans de nombreux mécanismes de défense des cellules cancéreuses contre l'apoptose représente une voie thérapeutique d'avenir. Nous en avons recherché dans les champignons endophytes de plantes péruviennes, ces micro-organismes produisant de nombreux métabolites de défense des plantes hôtes. Ce travail de thèse a d'abord porté sur l'isolement, la culture, l'identification, l'extraction et la caractérisation des souches de champignons endophytes. Les analyses statistiques effectuées sur ces extraits avec les résultats obtenus en HPLC ont confirmé les problèmes de variabilités qualitative et quantitative pouvant être rencontrés au cours de la culture des endophytes et décrites dans la littérature. La seconde partie expérimentale a porté sur la recherche de furocoumarines dans les extraits obtenus, en raison de leur potentiel effet inhibiteur sur la SOD. Nous avons dérépliqué ces composés dans les extraits d'endophytes au cours de deux stratégies de spectrométrie de masse réalisées en mode d'ionisation négatif. La première approche, à l'aide d'un QTOF, a abouti à l'identification de deux furocoumarines, la 5-Methyl-4H-furo[2,3-b][1]benzopyran-4-one et la déhydropachyrrhizone. La seconde, à l'aide d'un OrbiTrap, a vu l'identification de quatre autres furocoumarines : l'Ochrocarpine A, la Moellendorffiline, l'Anisolactone et l'Anhydrorutarétine .Afin de compléter cette approche métabolomique et identifier les molécules inhibitrices de la SOD, nous avons tenté de mettre au point un test d'activité de cette enzyme, rapide, peu coûteux et réalisable en routine. Nous avons sélectionné le test au pyrogallol, mais celui-ci n'a pas démontré les qualités recherchées tant au niveau de la sensibilité que de la reproductibilité. Nous orientons à présent les recherches vers des approches différentes, la recherche directe d'adduits sur la SOD par LC-MSSuperoxide dismutase is one of the major proteins controlling the oxidizing stress and cellular homeostasis. It is involved in numerous cancer cells proliferation processes. This protein is considered as major anti-cancer target for the development of new anti-cancer drugs. The goal of this work, was to research and identify an inhibitor of the SOD in endophytic fungi from Peruvian plants. These micro-organisms are known to produce numerous metabolites for host plants protection. During the preparation of endophytic extracts and their characterization by HPLC and statistical analyzes, we have pointed out a high quantitative and qualitative variability of the chemical content of endophytic extracts inside a same strain. Considering the literature we have focused our work on the identification of furocoumarins because of their potential inhibitory effect on the SOD. For this purpose two mass spectrometry strategies using negative ionization mode were carried out. With the QTOF mass spectrometer we have identified Methyl-4H-furo [2,3-b] [1] benzopyran-4-one and the déhydropachyrrhizone. With the OrbiTrap, the Ochrocarpine A, Moellendorffiline the Anisolactone and the Anhydrorutarétine were identified. Biological evaluation of the different extracts was performed using pyrogallol test. This investigation did not allow us to identify an inhibitor of the SOD. In the future we may consider seeking SOD inhibitors by looking at the formation SOD-chemical compound adducts using an LC-MS investigation
21
Cheung, Suet-ting, and 張雪婷. "Effects of superoxide dismutase 1 on frontal cortical neurons." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42924650.
Full text
22
Cheung, Suet-ting. "Effects of superoxide dismutase 1 on frontal cortical neurons." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42924650.
Full text
23
Samai, Mohamed. "Novel superoxide dismutase mimetics for protection against paraquat nephrotoxicity." Thesis, University of Brighton, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485754.
Full textAbstract:
Paraquat (PO), a broad-spectrum herbicide, is primarily eliminated from the body unchanged via the kidneys. Unfortunately, it is nephrotoxic; and the PO-induced nephrotoxicity involves severe renal damage caused by reactive oxygen species (ROS), specifically by increasing superoxide anion (0/-) generation in the kidney. While proven to be of benefit in animal models of organ injury involving O2.-, superoxide dismutase (SOD) and superoxide dismutase mimetics (SOOm) can suffer problems regarding their bioavailability and toxicity. Since ROS has been incriminated in the pathogenesis of several disease conditions, the search for ideal SOOm therefore continues unabated. Thus, the current study was undertaken with the overall objective of investigating and comparing the therapeutic potentials of Mn (II) and Cu (II) complexes of ethylenebis (oxyethylenenitrilo) tetraacetic acid (EGTA) and ethylenebis hydroxyphenylglycine (EHPG), novel SOOm, against PO-induced nephrotoxicity using in vitro and in vivo models. The reno-cytotoxic effects of PO on confluent NRK-52E renal cell line in the absence and presence of SOOm were assessed using biochemical assays of cellular viability and cell death. The mode of injury produced by PO in vitro was evaluated using Hoechst-Propidium iodide staining. The ability of PO to increase ROS generation, specifically O2.- and hydroxyl radicals (OW) was investigated using nitroblue tetrazolium reduction/hydroxyethidium fluorescence and deoxyribose assay respectively. ROS-mediated cell damage was assessed via determination of lipid peroxidation, inhibition of DNA and protein synthesis, DNA single strand breaks and poly- (AOP-ribose) polymerase (PARP) activation using the thiobarbituric acid reactive substance assa¥., cellular incorporation of [3H]-thymidine and [3H]-leucine, a DNA precipitation and [ H]-NAO incorporation assays respectively. In addition, the effects of PO on the renal activities and expression of SOD, catalase (CAT) and glutathione peroxidase (GSH-Px) in confluent NRK-52E renal cells in culture were also evaluated. The reno-cytotoxic effects of paraquat were mediated in part by oxidative stress injury secondary to increase generation of ROS; specifically 0/- and OW. This was accompanied by a reduction in the activity and expression of SOD, a reduction in the activity with no significant change in the expression of CAT and an increased in the activity of GSH-Px. Oxidative stress injury was further confirmed by increased lipid peroxidation, inhibition of DNA and protein synthesis, and increased DNA single strand breaks with a subsequent increased in PARP activation. The doses of paraquat examined predominantly produced necrotic cell death. EUK-134 (30-300 IJM), tempol (0.1-1.0 mM) and Mn (II) and Cu (II) complexes of EGTA (10100 IJM) and EHPG (10-100 IJM) were able to improve cellular viability and reduce PO-mediated cell death in vitro via dismutation and/or scavenging of O2.- and reduced OH· generation. Mn (II) complexes displayed greater efficacy than Cu (II) complexes and at equivalent concentrations, Mn (II)-EHPG provided greatest protection. Thus, the hypothesis that, these novel SOOm, particularly Mn (II) complexes of EHPG and EGTA, could provide similar beneficial effect in vivo was tested in rodent model of paraquat-induced nephrotoxicity. Administration of a single intraperitoneal dose of PO (10-100 mg/kg) to male wistar rats (weighing 200-250 g) produced acute renal failure (ARF) within 24-48 hours as evidenced by a significant increase in serum creatinine levels and fractional excretion of sodium (FENa) and a concomitant reduction in creatinine clearance. Unlike Mn (II)-EGTA (2 mg/kg), Mn (II)-EHPG (4 mg/kg) was able to significantly attenuate the PO-induced ARF. In contrast to SOD and/or conventional SOOm which can display pro-oxidant actions at higher concentrations these complexes were not toxic at the doses examined. Since the clinical toxicity profiles of EGTA and EHPG are already known, these novel SOOm particularly Mn (II)-EHPG could be beneficial in attenuating disease conditions involving ROS generation.
24
MacKenzie, Andrew. "Protection of vascular nitric oxide by superoxide dismutase mimetics." Thesis, University of Glasgow, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.266683.
Full text
25
Münch, Christian. "Initiation and propagation of mutant superoxide dismutase 1 misfolding." Thesis, University of Cambridge, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609791.
Full text
26
Ma, Huaibo. "Modeling the Structure and Mechanism of Nickel Superoxide Dismutase." Ohio University / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1303327993.
Full text
27
Durazo, Armando. "Hydrogen/deuterium exchange studies on copper-zinc superoxide dismutase." Diss., Restricted to subscribing institutions, 2007. http://proquest.umi.com/pqdweb?did=1495960591&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full text
28
Trist, Benjamin. "Superoxide dismutase 1 in the aetiology of Parkinson’s disease." Thesis, The University of Sydney, 2019. http://hdl.handle.net/2123/20579.
Full textAbstract:
Parkinson’s disease is the most common neurodegenerative movement disorder worldwide, and is the fastest growing neurological disease ahead of Alzheimer’s disease. Characteristic motor dysfunction results from the selective death of dopamine neurons in the substantia nigra pars compacta, however the aetiology of this neuron loss remains unknown. As such, current treatments help to alleviate Parkinsonian motor symptoms, but none are able to slow or halt the rate of dopaminergic neuron loss. A greater understanding of the molecular pathways leading to dopamine neuron death will accelerate the development of disease-modifying treatments that slow or halt neurodegeneration in this disorder. This thesis focusses on three focal points within the parkinsonian degenerative cascade; oxidative stress, copper dyshomeostasis, and protein misfolding, and aims to introduce the antioxidant copper-binding protein, superoxide dismutase 1 (SOD1), as an important nexus between these key pathologies. I describe, for the first time, misfolding and dysfunction of SOD1 localized to degenerating brain regions in Parkinson’s disease, which is significantly associated with both Lewy proteinopathy and neuron death in these regions. Importantly, I provide evidence that the development of this pathology precedes nigral dopamine neuron loss, and is therefore likely to be a causative factor in, rather than a result of, neurodegeneration in Parkinson’s disease. The sole use of post-mortem tissues within this study ensured any identified biochemical changes accurately reflected endogenous changes occurring within PD and ALS patients; a major criticism of current model systems aiming to recapitulate PD and ALS pathology. My work proposes SOD1 may constitute a novel target for therapeutic interventions aiming to slow the rate of dopaminergic neuron loss in Parkinson’s disease. Novel SOD1 proteinopathy in the Parkinson’s disease brain bears remarkable similarities to neurotoxic SOD1 proteinopathy in a proportion of familial amyotrophic lateral sclerosis (fALS) patients, suggesting similar pathways to neuron death in both disorders. The absence of SOD1 gene mutations in Parkinson’s disease patients exhibiting substantial SOD1 proteinopathy strengthens data from SOD1-fALS research demonstrating that non-genetic factors play key roles in SOD1 misfolding and dysfunction, especially biometal dyshomeostasis and oxidative stress. I demonstrate that these factors may also underlie the misfolding of soluble wild-type SOD1 protein in the vulnerable ventral spinal cord in non-SOD1-fALS and sALS patients, and propose that SOD1 toxicity arises in these patients irrespective of the formation of large insoluble misfolded SOD1 deposits. Importantly, shared pathways to neurodegeneration in Parkinson’s disease and ALS identified within this thesis highlight the potential for the translation of therapeutic approaches targeting SOD1, already in clinical trials for ALS, into disease-modifying therapies for Parkinson’s disease.
29
Moon, Bok Hee. "A study of the activity and characteristics of superoxide dismutase in the male reproductive parts of Petunia : a thesis submitted in partial fulfillment of the requirements for the degree of Master of Science in Plant Biotechnology in the School of Biological Sciences, University of Canterbury /." Thesis, University of Canterbury. Biological Sciences, 2006. http://hdl.handle.net/10092/1326.
Full textAbstract:
In the stamen (male reproductive tissue) of petunia 'Hurrah' flowers, the occurrence of SOD (superoxide dismutase) provided an effective anti-oxidative mechanism against superoxide production. Superoxide production and SOD activities at five developmental stages showed a positive correlation. The highest superoxide production and SOD activity in different parts of the stamen (anther, filament and pollen) were at stages with high metabolic activity: (i) during growing buds (in anthers and filaments) (ii) when flowers with predehiscent anthers were fully open (in pollen). In all parts of the stamen, SOD activity was the lowest at stage five (fully open flowers with dehiscent anthers), superoxide production was also lower at this stage with the exception of the pollen. The highest SOD activity was localized in anthers with the pollen, suggesting that the filaments only have a structural support function. SOD was examined on a native PAGE with regard to the isozymes present within the stamen of five developmental stages. Three isozymes, which were identified as Mn SOD, Fe SOD and Cu/Zn SOD by reactions with inhibitors, were commonly found at five developmental stages in crude extracts of anthers, filaments and pollen. The developmental stages with stronger isozyme bands on the native PAGE were consistent with the stages with higher SOD activities, and the Mn SOD and Fe SOD isozyme bands were more intense than Cu/Zn SOD bands, suggesting the activities of Mn SOD and Fe SOD in the crude extracts were much higher than Cu/Zn SOD. SOD from 1,000 stamens of dehiscent mature flowers was partially purified using ammonium sulphate fractionation and DEAE cellulose column chromatography. The purified bound fraction contained only one SOD isozyme on a native PAGE, which was shown to be a Mn SOD, as it is sensitive to neither hydrogen peroxide nor cyanide. The specific activity of the purified SOD was 66.5 U/mg and the yield of total activity was 3.0%. The progress of enzyme purification was monitored using SDS-PAGE and the bound fraction contained two major polypeptide bands. The purified enzyme activity was optimal in the range of neutral pH, but it was the highest at pH 7.8. Through incubation at various pH levels for 24 hours, favourable stability of the purified fraction was confirmed around a pH range of 7 to 8.5. The purified enzyme retained 87% of its initial activity at -20 ? after one month of storage, but at 4 ? only 38% of the initial activity remained after the same period of storage.
30
Corvo, Maria Luisa Teixeira de Azevedo Rodrigues. "Liposomes as delivery system for superoxide dismutase in experimental arthritis = Liposomen als dragersystemen voor superoxide dismutase in experimental artritis : Lipossomas come sistema terapêutico para superóxido dismutase na artrite experimental /." [S.l. : s.n.], 1998. http://www.gbv.de/dms/bs/toc/300314604.pdf.
Full text
31
Tew, D. G. "Some reactions of spin traps." Thesis, University of Oxford, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.355814.
Full text
32
Bendall, Jennifer Kate. "Physiology and pathophysiology of cardiac NADPH oxidase." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289766.
Full text
33
Sinaceur, Jamal Eddine. "Importance des dérivés réduits de l'oxygène dans l'intoxication alcoolique chez le rat : rôle de la desferrioxamine /." Paris : la Documentation française, 1987. http://catalogue.bnf.fr/ark:/12148/cb34926442c.
Full text
34
Bond, Christopher J. "Regulation, structure and folding of enzymes /." Thesis, Connect to this title online; UW restricted, 2000. http://hdl.handle.net/1773/9247.
Full text
35
Bergemalm, Daniel. "Mutant superoxide dismutase-1-caused pathogenesis in amyotrophic lateral sclerosis." Doctoral thesis, Umeå : Umeå university, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-31116.
Full text
36
Greenleaf, William Bruce. "Proton transfer in catalysis by iron and manganese superoxide dismutase." [Gainesville, Fla.] : University of Florida, 2004. http://wwwlib.umi.com/cr/ufl/fullcit?p3136943.
Full textAbstract:
Thesis (Ph.D.)--University of Florida, 2004.Typescript. Title from title page of source document. Document formatted into pages; contains 94 pages. Includes Vita. Includes bibliographical references.
37
Pramatarova, Albéna. "Role of CuZn superoxide dismutase in familial amyotrophic lateral sclerosis." Thesis, McGill University, 1999. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=36684.
Full textAbstract:
Amyotrophic lateral sclerosis (ALS) is a late onset neuro-degenerative disorder characterized by highly selective death of large motor neurons in the cerebral cortex and spinal cord. A proportion of the familial cases (FALS) with autosomal dominant transmission was linked to chromosome 21q and the defective gene was shown to be the Cu/Zn superoxide dismutase gene (SOD1). SOD1 is a ubiquitously expressed cytoplasmic metalloenzyme catalyzing the dismutation of the superoxide free radical into hydrogen peroxide and molecular oxygen. We have screened our FALS patients for mutations in the SOD1 gene and found mutations in about 13% of the cases. All but one mutation were single base pair substitutions resulting in amino acid changes (i.e. missense mutations) predicted to produce structurally defective molecules, and some of which significantly reduced the SOD1 enzyme activity in lymphoblasts. We have also identified a two base pairs deletion, which introduces a premature stop codon at position 131 and is predicted to result in the translation of a truncated molecule.It has been hypothesized that the pathology observed in FALS cases with SOD1 mutations is due to a gain of a new deleterious function of the mutant enzyme and not to a simple loss of dismutase activity. However the exact mechanism of SOD1 toxicity is still unknown and the specificity of the degenerating cell populations remains to be addressed. In this work, we investigated whether the damage seen in ALS with SOD1 mutations results from direct motor neuron toxicity. We have generated transgenic animals carrying a human SOD1 cDNA with the G37R mutation associated with FALS, driven by the neurofilament light chain promoter in order to specifically express the mutant protein in neuronal tissues. We show that transgenic animals express high levels of the human SOD1 protein in neuronal tissues, especially in the spinal cord where the motor neurons are concentrated, but develop no apparent motor deficit at up to 2 years of age. Our animal model suggests that neuron specific expression of mutant human SOD1 might not be sufficient for the development of the disease in mice, and hints towards the involvement of additional yet unidentified cell types/mechanisms.
38
Velishala, Shambhavi. "Computational Evaluation of Mechanistic Pathways of Action of Superoxide Dismutase." Youngstown State University / OhioLINK, 2012. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1364395885.
Full text
39
Lai, Kun-Nan. "Cloning and expression of cambialistic Bacteroides fragilis superoxide dismutase gene." Diss., This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-05042006-164528/.
Full text
40
Gustafson, Heather Lynn. "Role of Manganese Superoxide Dismutase in Chemotherapy-induced Oxidative Stress." Diss., The University of Arizona, 2011. http://hdl.handle.net/10150/203510.
Full textAbstract:
Existing treatments for mantle cell lymphoma (MCL) are non-curative, demonstrating a need for a refined treatment approach. Recent clinical trials have shown promising results with the use of mammalian target of rapamycin inhibitors. I hypothesize that the anti-tumor effect of mTOR inhibitors in mantle cell lymphoma is mediated by an increase in manganese superoxide dismutase (MnSOD) protein expression and accumulation of hydrogen peroxide (H₂O₂). Findings indicate that the rapamycin-induced cytostatic effect is characterized by increased levels of MnSOD and H₂O₂, and is necessary for the full growth inhibitory effect of rapamycin. Furthermore, over-expression of MnSOD elevated the level of H₂O₂ and increased sensitivity to MnSOD. Treatment with rapamycin resulted in a loss of serine 473 phosphorylation of AKT and increased levels of MnSOD were found to be due to inhibition of the mTORC2 complex. These results are the first to suggest that long term treatment of MCL cells with rapamycin inhibits the mTORC2 complex. By understanding the key signaling molecules and affected pathways in the anti-tumor effects of mTOR inhibitors, we may be able to identify additional predictive markers to improve the therapeutic value, or study drug combinations that will enhance the effect of ROSinduced cytotoxicity. A retrospective study utilizing samples from lymphoma patients receiving standard anthracycline-based therapies, identified single nucleotide polymorphisms in oxidative stressrelated genes associated with survival. Individuals carrying minor allele SNPs in myeloperoxidase (MPO) and an aldo-keto reductase (AKR1C3) were found to be associated with shorter time to disease progression and death. This data suggest that some patients may benefit from a different therapy than the current standard of care and that regulation of the redox environment plays a role in aggressive lymphoma treatment response.
41
Gu, Cong. "Superoxide Dismutase C Modulates Macropinocytosis and Phagocytosis in Dictyostelium Discoideum." FIU Digital Commons, 2018. https://digitalcommons.fiu.edu/etd/3887.
Full textAbstract:
Macropinocytosis and phagocytosis, two actin-dependent and clathrin independent events of endocytosis, enable the cells such as macrophages and neutrophils to either internalize pathogens and initiates the human innate immune response or serve as a direct entry route for productive infection of pathogen. Dictyostelium discoideum, soil-living amoeba, a unicellular eukaryote that could professionally internalize fluid phase or particles several folds more than that of macrophages and neutrophils. Additionally, multiple key signaling pathways are conserved between Dictyostelium and mammalian cells, including pathways affecting small GTPases Ras and Rac and their downstream effectors, and F-Actin remodeling. All these traits makes Dictyostelium an excellent model organism to study the process pf macropinocytosis and phagocytosis.
Upon internalization of the prey, these macropinocytes and phagocytes are often in an environment of increased production of superoxide radicals in the prey-containing vesicles, which helps stimulates the downstream signaling pathways to digest the prey inside. However, the mechanism of how superoxide regulates the process of macropinocytosis and phagocytosis is not fully understood. We had previously reported that Dictyostelium cells lacking Superoxide dismutase C (SodC) exhibited aberrantly high level of active RasG, high basal level of Phosphatidylinositol-3,4,5-triphosphate (PIP3), and severe chemotaxis defects. Now we report that sodC- cells displayed aberrant endosomal vesicle trafficking, significantly compromised particle uptake and defective cell to substratum matrix adhesion compared to that of wild type cells. By using high resolution live imaging microscope we also show that sodC- cells have defects in F-Actin remodeling at the phagocytic rim extension and F-Actin depolymerization of the nascent phagosome. Interestingly, the introduction of overexpressing of cytoplasmic superoxide dismutase (SodA), redox insensitive RasG (C118A) or treatment of PI3K inhibitor LY294002 in sodC- cells significantly rescued the defects of endosomal vesicle trafficking, particle uptake and adhesion. This project suggests that superoxide dismutase C regulates the endosomal vesicle trafficking, phagocytosis and cell to substratum matrix adhesion through the RasG/PI3K signaling axis in Dictyostelium cells.
42
Bouvet, Jean. "Superoxide dismutase mimics : an integrated approach from chemical design to bioactivity in cells." Electronic Thesis or Diss., Sorbonne université, 2023. https://accesdistant.sorbonne-universite.fr/login?url=https://theses-intra.sorbonne-universite.fr/2023SORUS583.pdf.
Full textAbstract:
Les superoxydes dismutases (SODs) sont des métalloenzymes, présentent dans l’ensemble du règne vivant, jouant un rôle crucial dans les défenses antioxydantes. En effet, elles régulent la concentration de l’anion superoxyde qui est un dérivé réactif de l’oxygène et un sous-produit naturel du métabolisme de celui-ci. Dans certaines maladies, comme les maladies inflammatoires chroniques de l’intestin, il a été montré une déficience des défenses antioxydantes et en particulier des SODs. En conséquence, une augmentation des espèces réactives de l’oxygène est observée (stress oxydant) qui serait impliquées dans la pathogénèse. L'utilisation de complexes métalliques mimant la SOD et son activité catalytique pourrait constituer une solution prometteuse dans le traitement de cette maladie inflammatoire et celles liées, de près ou de loin, au stress oxydant. Dans une première partie, des mimes de SOD ont été développés en s’appuyant sur une approche biomimétique. Une première stratégie basée sur des complexes peptidiques cherchant à imiter les différentes sphères de coordination des enzymes endogènes a été suivie. Pour ce faire, des peptides s’autoassemblant en homotrimères d’hélices alpha ont été modifiés afin d’insérer un site de coordination au cœur de la structure, similaire à celui de la SOD1. Ils ont été caractérisés et possèdent une activité anti-superoxyde. Afin de se rapprocher au plus près des sites actifs naturels, une asymétrisation a ensuite été réalisée par le biais d’hétérotrimères ce qui a exacerbé l’activité. Une seconde stratégie fondée sur l’utilisation de petites molécules telles que Mn1, un complexe à base de Mn reproduisant le site actif de la SOD2 et son activité, a été explorée. Ce complexe avait préalablement démontré une activité anti-inflammatoire sur cellules et sur modèle murin. Un nouvel analogue Mn1IP a en particulier été étudié. Il a pu être montré qu’il possédait une bio-activité équivalente. Dans le but d’obtenir d’avantage d’informations sur la spéciation cellulaire de Mn1 et de ses dérivés, leurs ligands ont été marqués avec du brome. Les molécules en découlant ont été caractérisées et un premier essai en imagerie de fluorescence X a pu être réalisé. Dans une seconde partie, nous avons d’abord cherché à évaluer le stress oxydant sur un modèle cellulaire épithélial intestinal de l’inflammation à l’aide de différentes sondes connues dans la littérature. Le lipopolysaccharide (LPS) bactérien classiquement utilisé pour déclencher l’inflammation n’a pas montré une augmentation du stress oxydant contrairement à d’autres générateurs d’espèces réactives de l’oxygène. Cette absence d’augmentation a été attribuée au fait que le stress oxydant généré par le LPS était probablement trop faible sur ce modèle pour être quantifiable de cette manière. Dans un second temps, nous avons exploré plus en détail la réponse cellulaire après exposition au LPS au travers de l’expression protéique et génomique de plusieurs entités biologiques jouant un rôle prépondérant dans l’inflammation et le stress oxydant, toutes étant liées aux maladies inflammatoires chroniques de l’intestin. Il a pu être montré que la dérégulation d’expression induite par le LPS était partiellement ou totalement jugulée lorsque Mn1 était incubé conjointement. Dans un troisième temps, nous avons développé une stratégie de criblage à haut débit par imagerie métabolique pour la découverte de mimes de SOD. Cette méthode réduit fortement le temps nécessaire pour la caractérisation des effets biologiques de nouvelles molécules puisqu’un grand nombre de composés peut être testé au même moment sur une large gamme de concentrations. Finalement, nous avons analysé de nouveau des données transcriptomiques de la littérature sur des patients atteints de la maladie de Crohn et nous avons pu montrer que des voies du stress oxydant étaient impliquées à la fois dans la maladie mais également dans la rechute des patients après traitement opératoireSuperoxide Dismutases (SODs) are metalloenzymes present throughout all the kingdoms of life, playing a crucial role in antioxidant defence. They regulate the concentration of superoxide anion, a reactive oxygen species and a natural by-product of oxygen metabolism. In certain diseases, such as chronic inflammatory bowel diseases, it has been shown that antioxidant defences are weakened, in particular SODs. As a result, an increase in reactive oxygen species (oxidative stress) is observed, which is thought to be involved in pathogenesis. To compensate for the deficiency of SODs, the use of metal complexes mimicking their catalytic activity could be a promising solution in the treatment of this inflammatory disease and others, closely or remotely linked to oxidative stress. In the first part, SOD mimics were developed using a biomimetic approach. A first strategy based on peptide complexes seeking to mimic the different coordination spheres of endogenous enzymes was followed. To this end, peptides self-assembling into alpha-helix homotrimers were modified to insert a coordination site at the heart of the structure, similar to that of SOD1. They have been characterized and showed anti-superoxide activity. In order to get as close as possible to the natural active sites, asymmetrization was then performed using heterotrimers, which exacerbated the activity. A second strategy, based on the use of small molecules such as Mn1, a Mn-based complex reproducing the SOD2 active site and its activity, was explored. This complex had previously demonstrated anti-inflammatory activity in cell and mouse models. In particular, a new Mn1IP analogue, which had a less toxic ligand but was also less active, was studied. It was shown to have equivalent bioactivity. In order to gain further information on the cellular speciation of Mn1 and its derivatives, their ligands were labelled with bromine. The resulting molecules were characterized and an initial X-ray fluorescence imaging experience was carried out. Other small molecules were also studied. In a second part, we first sought to assess oxidative stress in an intestinal epithelial cell model of inflammation using various probes known from the literature. The bacterial lipopolysaccharide (LPS) classically used to trigger inflammation did not show an increase in oxidative stress, unlike other reactive oxygen species generators. This lack of increase was attributed to the fact that the oxidative stress generated by LPS was probably too low in this model to be quantifiable in this way. In a second step, we explored in greater detail the cellular response after LPS exposure through protein and genomic expression of several biological entities playing a prominent role in inflammation and oxidative stress, all of which are linked to chronic inflammatory bowel diseases. It was shown that LPS-induced expression deregulation was limited when Mn1 was co-incubated. Thirdly, we developed a high-throughput metabolic imaging screening strategy for the discovery of SOD mimics. This method greatly reduces the time needed to characterize the biological effects of new molecules, since a large number of compounds can be tested at the same time over a wide range of concentrations. Finally, we re-analysed transcriptomic data from the literature on Crohn's disease patients and were able to show that oxidative stress pathways were involved both in the disease and in the relapse of patients after operative treatment
43
Bu, Jia-Ying J. "Isolation, reconstitution, and molecular cloning of the manganese-containing superoxide dismutase from Deinococcus radiodurans." Diss., This resource online, 1992. http://scholar.lib.vt.edu/theses/available/etd-09042008-063623/.
Full text
44
Peters, J. Andrew. "An investigation into the mechanism of 2-oxohistidine formation from the peroxidase activity of superoxide dismutase." Morgantown, W. Va. : [West Virginia University Libraries], 2002. http://etd.wvu.edu/templates/showETD.cfm?recnum=2479.
Full textAbstract:
Thesis (M.S.)--West Virginia University, 2002.Title from document title page. Document formatted into pages; contains ix, 67 p. : ill. Includes abstract. Includes bibliographical references (p. 63-67).
45
Deitrich, Christian L. "Production, characterization and use of isotopically enriched metalloproteins for the analysis of biological samples by species-specific isotope dilution ICP-MS." Thesis, University of Aberdeen, 2009. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=25802.
Full textAbstract:
In this work, the chemical preparation and characterization of an isotopically enriched superoxide dismutase (SOD) is described. Its evaluation as a standard in species-specific isotope dilution analysis by HPLC coupled to ICP-MS is carefully evaluated. The proposed method involved the removal of the enzyme's metal co-factors under various conditions and their replacement with isotopically enriched ⁶⁵Cu and ⁶⁸Zn. SEC-ICP-MS showed that the prepared enriched enzymes had a different metal isotopic abundance compared to the wild-type enzyme. Isotopically enriched and wild-type SOD showed the same migration pattern in 1D-PAGE. An enzyme activity assay provided evidence that incorporated ⁶⁵Cu was bound to the correct SOD-binding motif, since the measured activity correlated directly with the amount of Cu present in the prepared enzyme. The addition of free Cu and Zn or a metal chelator did not result in any exchange or loss of metals from the enzyme at neutral pH. Striking experiments were undertaken to evaluate the use of isotopically enriched SOD in SS-IDMS. The chemical preparation study on SOD was further extended to prepare various other isotopically enriched metalloproteins, including carbonic anhydrase, ceruloplasmin, transferring and haemoglobin. Various enrichment procedures were conducted and their performances then evaluated, using SEC-ICP-MS and protein assays. A procedure for the quantification of SOD in tissue samples using an isotopically enriched SOD spike in combination with 2-dimensional HPLC and SS-IDMS was developed and assessed. The feasibility of employing isotopically enriched protein spikes for the speciation of metalloproteins by utilising gel electrophoresis and LA-ICP-MS was also investigated. Furthermore, the change of the iron speciation of the meat-containing protein myoglobin after various treatments was examined using a combination of SEC-ICP-MS and ESI-MS.
46
Forsberg, Karin. "Misfolded superoxide dismutase-1 in sporadic and familial Amyotrophic Lateral Sclerosis." Doctoral thesis, Umeå universitet, Patologi, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-47550.
Full textAbstract:
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative syndrome of unknown etiology that most commonly affects people in middle and high age. The hallmark of ALS is a progressive and simultaneous loss of upper and lower motor neurons in the central nervous system that leads to a progressive muscle atrophy, paralysis and death usually by respiratory failure. ALS is not a pure motor neuronal syndrome; it extends beyond the motor system and affects extramotor areas of the brain as well. The majority of the patients suffer from a sporadic ALS disease (SALS) while in at least ten percent the disease appears in a familial form (FALS). Mutations in the gene encoding the antioxidant enzyme superoxide dismutase-1 (SOD1) are the most common cause of FALS. More than 165 SOD1 mutations have been described, and these confer the enzyme a cytotoxic gain of function. Evidence suggests that the toxicity results from structural instability which makes the mutated enzyme prone to misfold and form aggregates in the spinal cord and brain motor neurons. Recent studies indicate that the wild-type human SOD1 protein (wt-hSOD1) has the propensity to develop neurotoxic features. The aim of the present study was to investigate if wt-hSOD1 is involved in the pathogenesis of SALS and FALS patients lacking SOD1 mutations and to evaluate the neurotoxic effect of misfolded wt-hSOD1 protein in vivo by generating a transgenic wt-hSOD1 mice model. We produced specific SOD1-peptide-generated antibodies that could discriminate between the misfolded and native form of the enzyme and optimized a staining protocol for detection of misfolded wt-hSOD1 by immunohistochemistry and confocal microscopy of brain and spinal cord tissue. We discovered that aggregates of misfolded wt-hSOD1 were constitutively present in the cytoplasm of motor neurons in all investigated SALS patients and in FALS patients lacking SOD1 gene mutations. Interestingly, the misfolded wt-hSOD1 aggregates were also found in some motor neuron nuclei and in the nuclei of the surrounding glial cells, mainly astrocytes but also microglia and oligodendrocytes, indicating that misfolded wt-hSOD1 protein aggregates may exert intranuclear toxicity. We compared our findings to FALS with SOD1 mutations by investigating brain and spinal cord tissue from patients homozygous for the D90A SOD1 mutation, a common SOD1 mutation that encodes a stable SOD1 protein with a wild-type-like enzyme activity. We observed a similar morphology with a profound loss of motor neurons and aggregates of misfolded SOD1 in the remaining motor neuron. Interestingly, we found gliosis and microvacuolar degeneration in the superficial lamina of the frontal and temporal lobe, indicating a possible frontotemporal lobar dementia in addition to the ALS disorder. Our morphological and biochemical findings were tested in vivo by generating homozygous transgenic mice that over expressed wt-hSOD1. These mice developed a fatal ALS-like disease, mimicking the one seen in mice expressing mutated hSOD1. The wt-hSOD1 mice showed a slower weight gain compared to non-transgenic mice and developed a progressive ALS-like hind-leg paresis. Aggregates of misfolded wt-hSOD1 were found in the brain and spinal cord neurons similar to those in humans accompanied by a loss of 41 % of motor neurons compared to non-transgenic litter mates. In conclusion, we found misfolded wt-hSOD1 aggregates in the cytoplasm and nuclei of motor neurons and glial cells in all patients suffering from ALS syndrome. Notable is the fact that misfolded wt-hSOD1 aggregates were also detected in FALS patients lacking SOD1 mutations indicating a role for SOD1 even when other genetic mutations are present. The neurotoxicity of misfolded wt-hSOD1 protein was confirmed in vivo by wt-hSOD1 transgenic mice that developed a fatal ALS-like disease. Taken together, our results support the notion that misfolded wt-hSOD1 could be generally involved and play a decisive role in the pathogenesis of all forms of ALS.
47
Seto, Nina O. L. "Cloning and expression of the Drosophila melanogaster CuZn superoxide dismutase gene." Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/30971.
Full textAbstract:
Aging and disease processes may be due to deleterious and irreversible changes produced by free radical reactions. The enzyme copper-zinc superoxide dismutase (CuZn SOD; superoxide: superoxide oxidoreductase, EC 1.15.1.1) performs a protective function by scavenging superoxide radicals. In order to determine whether additional SOD activity affects longevity and oxygen metabolism in Drosophila, our approach was to clone the Sod gene and introduce additional copies of the gene back into the genome via P element mediated transformation. The effects of increased SOD activity on Drosophila life span and oxygen free radical metabolism were investigated.
The CuZn SOD cDNA and gene were cloned from Drosophila melanogaster. The sequence of the Sod cDNA and gene revealed an additional C-terminal triplet coding for valine not found in the mature SOD protein. The nucleotide sequence of the coding region has 56% and 57% identity when compared to the corresponding human and rat Sod genes, respectively. A probe of the cloned gene hybridizes to position 68A4-9 on Drosophila polytene chromosomes. In wild-type Drosophila the Sod cDNA hybridizes to a 0.7-0.8 kb transcript which is greatly diminished in a SOD 'null' mutant that produces only 3.5% of the SOD protein.
A 1.8 kb EcoRI gene fragment containing the Sod gene was cloned into the P vector pUChsneo and microinjected into Drosophila embryos. Five transformed lines, each of which contain an additional copy of the Sod gene at different chromosomal sites were constructed. The chromosomal positions of the transposed Sod sequence were determined by in situ hybridization of the Sod gene to salivary gland polytene chromosomes. Analysis of RNA from the transformed flies revealed that the transposed Sod gene was expressed. The range of SOD activity for the five transformed lines was 131% to 170% of the value of wild-type. There was good correlation between the amount of Sod mRNA and the level of SOD activity in the transformed lines.
Increased SOD levels in the transformed lines did not confer greater resistance to paraquat-generated superoxide radicals, nor increase their lifespan. The SOD 'null' mutant with 3.5% of the wild-type SOD activity was hypersensitive to paraquat when compared to wild-type, whereas the heterozygous SOD deficiency Df(3L)1xd⁹/TM3SbSer with 50% of the wild-type SOD activity was not. Mutants lacking SOD are dramatically impaired in oxygen metabolism and a few percent of wild-type activity appears to provide significant protection against superoxide, while 50% of the wild-type levels confers essentially the same resistance as wild-type. Despite the observation that the SOD activities found in a wide range of animals correlates directly with their longevity, Drosophila melanogaster appears to be well protected against the toxic effects of oxygen by its native levels of SOD.Arts, Faculty of
Philosophy, Department of
Graduate
48
Paramchuk, Wendy Jo-Ann. "Iron superoxide dismutase cDNAs of Leishmania chagasi, characterization and functional studies." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp04/mq24690.pdf.
Full text
49
Murnaghan, Julia M. W. "Winter survival in transgenic alfalfa (Medicago sativa L.) expressing superoxide dismutase." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0031/MQ47350.pdf.
Full text
50
Pramatarova, Albéna. "Role of Cu/Zn superoxide dismutase in familial amyotrophic lateral sclerosis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0030/NQ64647.pdf.
Full text