Dissertations / Theses on the topic 'Reactive oxygen species'
To see the other types of publications on this topic, follow the link: Reactive oxygen species.
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 'Reactive oxygen species.'
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
Smith, Cheryl. "Reactive oxygen species in atherosclerosis." Thesis, King's College London (University of London), 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.302549.
Full text
2
Stanczak, Anna. "Reactive oxygen species in laundry applications." Thesis, Durham University, 2018. http://etheses.dur.ac.uk/12885/.
Full textAbstract:
Chapter 1 is divided into two parts, the first gives a brief review of oxygen-based bleaching agents commonly used in powder laundry detergent with emphasis on the properties of hydrogen peroxide and peroxy acids. In the second part of the literature review, different methods of detection of Reactive Oxygen Species (ROS) are discussed. Chapter 2 discusses analytical techniques used throughout this thesis, mainly focusing on the fluorescence and UV-Vis spectroscopy, as well as imaging techniques: Image Analysis and Diffuse Reflectance Spectroscopy. This chapter provides also detailed experimental procedures. Chapter 3 includes the results and discussion part of the thesis. The process of the development of fluorescent probes for the most relevant ROS in laundry applications: hydrogen peroxide, peroxy acid, hydroxyl radicals and singlet oxygen is discussed. The established toolbox of molecular probes consists of: terephthalic acid, 9,10-anthracenediyl-bis(methylene)dimalonic acid and 2-naphthylboronic acid for detection of hydroxyl radicals, singlet oxygen and peroxides, respectively. Chapter 4 reports the kinetic parameters of the ROS generated from genuine bleach source in simplified model system (alkaline solution) established with the developed toolbox of molecular probes. Chapter 5 introduces four model dyes which represent genuine stains: curcumin, crocin, betanin and chlorophyllin. The impact of pH on the bleaching of the model dyes was investigated as well as bleaching kinetic parameters. The behaviour of peroxy acids generated from bleach sources in the presence of model dyes was determined with the toolbox of molecular probes developed in Chapter 3. Chapter 6 examines the bleaching performance of different ROS on genuine stains deposed on fabric: grass, tomato, curry, red wine and tea with Image Analysis technique and Diffuse Reflectance Spectroscopy. In the second part of the chapter the behaviour of the bleaching agents in the presence of stains was investigated.
3
Wu, Wan Man. "Reactive oxygen species and murine malaria." Thesis, The University of Sydney, 1992. https://hdl.handle.net/2123/26446.
Full textAbstract:
The aim of this study was to investigate the role of ROS in the protective and pathological immune response during malarial infection. For this purpose, four isolates of Plasmodium parasites (P. berghei ANKA, P. vinckei, P. berghei K152 and P. chabaudi) and two different inbred strains of mice (CBA and DBA) were used.
The patterns of mortality varied between the different mouseparasite strain combinatio ns. The mortality of CBA mice infected with P. vinckei and P. berghei K152, and DBA mice infected with P. berghei ANKA, related to the levels of parasitaemia. However early mortality of CBA mice infected with P. berghei ANKA did not relate to the parasitaem ia level but to the onset of neurologica l symptoms. Over 90% of P. chabaudi—infected CBA mice recovered from the infection.
The morphologi cal examinatio n of brain tissues obtained from P. berghei ANKA-infec ted CBA mice on day 7 post-inocul ation showed haemorrag e, oedema and the infiltration of mononucle ar cells. Measurement of the permeability of the blood-brain barrier by injection of Evans blue showed the dye leaking into the brain parenchyma, suggesting a dysfunction of the barrier in this mouse model.
The hypothesis that ROS play a role in the anti—malaria response was supported by previous studies demonstrati ng that malaria parasites are killed by ROS in vivo and in vitro (reviewed in Hunt & Stocker. 1990). To further test the hypothesis. the oxidative burst ability of splenic macrophage s and peripheral monocytes taken from different mouse-para site strain combinations was examined.
There was a significant increase of superoxide production by splenic macrophag es at the early stage of all the infections and the spleen weight gradually increased during all the infections. Furthermore, the oxidative burst ability of monocytes was significantly increased in the late stage of all the infections, which was accompanied by increased peripheral WBC numbers, especially in the numbers of monocytes and PMNs in all the infections except the P. berghei ANKA infection in CBA mice.
Of the four strains of parasites infecting CBA mice, the self-resol ving P. Chabaudi infection induced the greatest PMA-stimulable response superoxide anion production on certain days after parasite in inoculation in both splenic macrophages and monocytes . Conversely, the P. vinckei infection induced the lowest response, which may partly explain why the parasites generated faster in these mice than in the other three strains.
Malaria parasites are able to induce immunosup pression at the early stage of infection as shown by the decline in the total number of WBC and the decrease of superoxide production by monocytes. This immunosuppresion may help explain why the parasites can survive even when their numbers are. small.
TNF and IFN—y are known as major mediatory factors involved in the development of cerebral malaria. This was supported by the cytokine gene expression studies which showed that both TNF and IFN-y mRNAs were expressed in the brains of mice with cerebral malaria. These cytokines may stimulate mononuclear phagocytes to produce other soluble factors to cause cerebral damage.
ROS release d from mononuclear phagocytes are thought to be crucial factors involved in the development of cerebral malaria (Hunt et al., 1991). However , the oxidative burst ability of splenic macrophages and monocytes in the P. berghei—ANKA infected CBA mice, which suffered cerebral malaria and died early in the infection, was lower than that in the same infection in DBA mice which recovered from the cerebral lesion but died at a later stage of infection with a high level of parasitaemia. Further more, lipid peroxidation studies showed that there was no significant difference in brain MDA formation between control mice and the mice with cerebral malaria . These results fail to provide evidence for a role of ROS in the development of cerebral malaria . Further studies to investigate lipid peroxidation and redox. status of the brain in cerebral malaria using HPLC are required.
4
Yu, Tian-Wei. "Genotoxic damage induced by reactive oxygen species." Thesis, University of Surrey, 1997. http://epubs.surrey.ac.uk/764/.
Full text
5
Baumber, Julie. "Reactive oxygen species and equine sperm function /." For electronic version search Digital dissertations database. Restricted to UC campuses. Access is free to UC campus dissertations, 2003. http://uclibs.org/PID/11984.
Full text
6
Xie, Ruiyu. "Reactive Oxygen Species-Induced Necrotic Cell Death." Diss., The University of Arizona, 2009. http://hdl.handle.net/10150/195215.
Full textAbstract:
Mechanisms of cell death extend beyond the simple apoptosis/necrosis relationship to include regulated modes of cell death that do not readily fit either of the classic descriptors. One such mechanism of cell death involves poly(ADP-ribose)polymerase-1 (PARP-1)-mediated cell death. 2,3,5-Tris(Glutathion-S-yl)-hydroquinone (TGHQ), a reactive oxygen species (ROS) generating nephrotoxic and nephrocarcinogenic metabolite of hydroquinone, causes necrotic renal cell death, the basis for which is unclear. We therefore investigated TGHQ-mediated cell death in human renal proximal tubule epithelial HK-2 cells. TGHQ induced ROS generation, DNA strand breaks, hyperactivation of PARP-1, rapid depletion of nicotinamide adenine dinucleotide (NAD), elevations in intracellular Ca2+ concentrations, loss of mitochondrial membrane potential, and subsequent necrotic cell death. Interestingly, PARP-1 hyperactivation was not accompanied by the translocation of apoptosis-inducing factor (AIF) from mitochondria to the nucleus, a process usually associated with PARP-dependent cell death. Inhibition of PARP-1 with PJ34 blocked TGHQ-mediated accumulation of poly(ADP-ribose) polymers, NAD consumption, and the consequent necrotic cell death. However, HK-2 cell death was only delayed by PJ34, and cell death remained necrotic in nature. In contrast, chelation of intracellular Ca2+ with BAPTA-AM completely abrogated TGHQ-induced necrotic cell death. Ca2+ chelation not only prevented the collapse in the mitochondrial potential but also attenuated PARP-1 hyperactivation. Conversely, inhibition of PARP-1 modulated TGHQ-mediated changes in Ca2+ homeostasis. Moreover, TGHQ caused a sequential oxidation of peroxiredoxin III (PrxIII), a protein considered the primary antioxidant defense within mitochondria. Thus, TGHQ induced two acidic shifts in PrxIII, with both pI shifted spots representing oxidized forms of PrxIII. Transient expression of a dominant negative version of PrxIII resulted in a significant increase in TGHQ-induced cytotoxicity, whereas overexpression of wild-type PrxIII significantly attenuated cytotoxicity. Our studies provide new insights into PARP-1-mediated necrotic cell death. Changes in intracellular Ca2+ concentrations appear to couple PARP-1-hyperactivation to subsequent cell death, but in the absence of AIF release from mitochondria. NAD depletion, mitochondrial membrane depolarization, Ca2+-mediated calpain activation, and PrxIII oxidation, all contribute to TGHQ-driven ROS-mediated necrotic cell death.
7
Cowgill, Danielle Lee. "FIELD DECTION DEVICE OF REACTIVE OXYGEN SPECIES." DigitalCommons@CalPoly, 2013. https://digitalcommons.calpoly.edu/theses/1107.
Full textAbstract:
Traumatic brain injuries (TBIs) contribute to approximately 30.5% of all injury related deaths in the United States per year and approximately 1.7 million TBIs per year occur as an isolated injury or other injury. Military personnel are exposed to TBIs and have less availability to resources traditionally used to diagnose a TBI. Reactive oxygen species (ROS) play a large role in secondary traumatic brain damage, especially lipid peroxidation, following TBIs. One of the principle and most studied byproducts of lipid peroxidation is malondialdehyde (MDA). The focus of this paper was to create an initial proof-of-concept field diagnostic device to detect ROS, or constituents, following a TBI. The device was divided into three main sections: blood separation, sample separation, and detection. This thesis report examined the blood and sample separation sections of the device; however the blood separation was not developed due to university restrictions. Pre-fabricated microfluidic chips and a confocal microscope were used for the separation. Pressure was first used to drive the fluid through the channel to observe functionality of the chip with 10 um microspheres and then a MDA solution once the spheres were successful. When fluid successfully flowed through the channels with pressure, voltage was then applied to the channels to create a capillary electrophoresis (CE) system. The CE system was tested with the spheres first and then the MDA solution upon successful demonstration of voltage-driven flow. Analysis of the images was performed using ImageJ software in attempt to determine the velocity of the spheres and MDA. The results of the system appeared to successfully drive the MDA with voltage-driven flow after waiting for the residual effects of the applied pressure to reduce. However, any conclusions require more experimental data.
8
Yamamoto, Shinichiro. "Reactive Oxygen Species / Reactive Nitrogen Species-sensitive TRP channels : Molecular Activation Mechanism and Physiological Significance." 京都大学 (Kyoto University), 2008. http://hdl.handle.net/2433/124503.
Full text
9
Liu, Bin. "P53 AND REACTIVE OXYGEN SPECIES: A CONVOLUTED STORY." UKnowledge, 2007. http://uknowledge.uky.edu/gradschool_theses/450.
Full textAbstract:
The tumor suppressor p53 has a close relation with reactive oxygen species (ROS). As an indispensable component of the cellular redox system, ROS not only have been established to be involved in p53-dependent apoptosis, but also regulate p53 activity. Recent studies revealed several novel actions of p53, such as transactivation of antioxidative proteins, mitochondria translocation and inhibition of glycolysis. The fate of cells where p53 signaling pathways are initiated is either survival or death. In this review, we examine the hypothesis that ROS regulate cell fate through p53, in a way that physiological ROS levels trigger the protective pathways, while p53 behaves more like a cell killer under cytotoxic oxidative stress.
10
Lloyd, Daniel Robert. "Formation of DNA damage by reactive oxygen species." Thesis, Institute of Cancer Research (University Of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298187.
Full text
11
Mian, Kousar Bashir. "Inhibition of nitric oxide by reactive oxygen species." Thesis, University of Glasgow, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318114.
Full text
12
Pinto, Ana Filipa Carapinha. "Reductive scavenging of reactive oxygen species in prokaryotes." Doctoral thesis, Universidade Nova de Lisboa. Instituto de Tecnologia Química e Biológica, 2012. http://hdl.handle.net/10362/9918.
Full textAbstract:
Dissertação para a obtenção de grau de doutor em Bioquímica pelo Instituto de Tecnologia Química e Biológica. Universidade Nova de Lisboa.The purpose of this thesis is to contribute to a better understanding of systems involved in the scavenging of reactive oxygen species. The work focuses on an enzyme from the Rubrerythrin family that reduces hydrogen peroxide and one from the Superoxide Reductase family that reduces the superoxide anion. Both of these families are distributed widely across the three domains of life, Archaea, Bacteria and Eukarya, but are mainly found in anaerobic and microaerophilic prokaryotes.(...)
13
Bustami, Mona Ratib. "Reactive oxygen and nitrogen species in cystic fibrosis." Thesis, University of Bath, 2002. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.248100.
Full text
14
Soltau, Carl Peter. "Nitroxide trapping of radical species formed from the reaction of sulfoxides with reactive oxygen species." Thesis, Queensland University of Technology, 2021. https://eprints.qut.edu.au/210339/1/Carl_Soltau_Thesis.pdf.
Full textAbstract:
This project focussed on an in-depth evaluation of an established methodology that uses dimethyl sulfoxide (DMSO) as a reactive solvent with a profluorescent nitroxide (PFN) to detect and quantify particulate matter-derived ROS (Reactive Oxygen Species). Additionally, a novel approach which utilized cyclic sulfoxide tetrahydrothiophene-1-oxide (THTO) as the reactive solvent was investigated. The reactions of these sulfoxides with ROS generated from multiple sources in the presence of nitroxide radical scavengers were investigated. The results of these experiments show that nitroxides can display much broader reactivity than the simple radical scavenging processes that have previously been accepted.
15
Sun, Zhenning. "Studies on fluorescent probes for the specific detection of reactive oxygen species and reactive nitrogen species in living cells." View the Table of Contents & Abstract, 2006. http://sunzi.lib.hku.hk/hkuto/record/B36845395.
Full text
16
Hole, Paul Spencer. "Role of reactive oxygen species in ras-mediated leukaemogenesis." Thesis, Cardiff University, 2010. http://orca.cf.ac.uk/54355/.
Full textAbstract:
Mutations of Ras and activation of the Ras pathway are amongst the most common abnormalities detected in human cancer (-20%), and in myeloid neoplasia. In addition, excessive production of reactive oxygen species (ROS) is a common feature of human malignancy and is often triggered by activation of Ras oncogenes. ROS act as second messengers and can influence a variety of cellular process including growth factor responses and cell survival. This study examined the contribution of ROS production to the phenotype of mutationally-activated Ras in normal human CD34+ haematopoietic progenitor cells. For the first time, this study demonstrated that Ras strongly upregulated the production of both superoxide and hydrogen peroxide (H2O2) in these cells, through the stimulation of NOX oxidase activity, without affecting the expression of endogenous antioxidants or the production of mitochondrial ROS. Ras also promoted both the survival and the growth factor independent proliferation of CD34+ cells. Using oxidase inhibitors and antioxidants, it was found that excessive ROS production by these cells did not contribute to their enhanced survival rather, this study presents the first data demonstrating that ROS promoted their growth factor-independent proliferation. While Ras-induced ROS production specifically activated the p38MAPK oxidative stress response, this failed to induce expression of the cell cycle inhibitor pl6INK4A instead, ROS promoted the expression of cyclin Dl and D3. Expression of activated Ras in human haematopoietic progenitors drives hyperphosphorylation of PKC family members, which mediates several phenotypes of mutant Ras in haematopoietic cells including dysregulated development. This study demonstrated that endogenous H2O2 production contributes to hyperphosphorylation of PKC in this model, and that exogenous H2O2 can drive phosphorylation of PKC in a similar manner. Finally, this study presents preliminary data obtained by kinomic PepChip analysis suggesting that endogenous ROS production driven by mutant Ras can influence the kinase activity of these cells, consistent with the hypothesis that ROS may promote protein phosphorylation via phosphatase inhibition. In summary, this study presents novel data showing endogenous ROS production makes a significant contribution to the phenotype of human haematopoietic progenitor cells expressing mutant Ras and suggests that targeting ROS may be a valid approach in acute myeloid leukaemia therapy.
17
Hurd, 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 textAbstract:
This work investigates the reactions of proteins with ROS when mitochondria are exposed to H2O2 or when they generate ROS endogenously. Using isolated mitochondria, those proteins that are particularly sensitive to low concentrations of H2O2 and to ROS generated by the mitochondrial electron transport chain were first identified using a method called Redox-Difference Gel Electrophoresis (Redox-DIGE). Most redox sensitive thiol proteins identified by Redox-DIGE were involved either in fatty acid oxidation or in the regulation of the pyruvate dehydrogenase complex. Next the mechanisms by which ROS selectively oxidise mitochondrial thiol proteins were investigated; it was determined that H2O2 generated by the electron transport chain may either oxidise mitochondrial thiol proteins directly or indirectly, through oxidation of the peroxiredoxin and thioredoxin redox couples. To determine if ROS generated by mitochondria might act as a redox signal by altering the functions of mitochondrial proteins, the effect of protein thiol oxidation was tested on the activity of two proteins: pyruvate dehydrogenase kinase and propionyl-CoA carboxylase. Loss of pyruvate dehydrogenase kinase and propionyl-CoA carboxylase activity correlated with protein thiol oxidation and was very sensitive to ROS, suggesting a plausible mechanism of redox regulation of these proteins in vivo. Lastly, glutathionylation of complex I was investigated in intact mitochondria exposed to a glutathione oxidant; two cysteine residues on the 75 kDa subunit of complex I were shown to become glutathionylated. The functional effect of glutathionylation of these two cysteine residues on complex I activity is currently under investigation.
18
Cetinbas, Naniye. "Reciprocal regulation of glutamine metabolism and reactive oxygen species." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/45714.
Full text
19
Tatla, Sangeeta. "The role of reactive oxygen species in lymphocyte activation." Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244071.
Full text
20
Zeng, Zhen [Verfasser], Albert [Akademischer Betreuer] Gollhofer, and Daniel [Akademischer Betreuer] König. "Effects of dietary strategies on reactive oxygen species production." Freiburg : Universität, 2021. http://d-nb.info/1237617979/34.
Full text
21
Fisher, Helen M. "Mechanisms of reactive oxygen species generation by mammalian spermatozoa." Thesis, University of Edinburgh, 1995. http://hdl.handle.net/1842/20503.
Full textAbstract:
The generation of reactive oxygen species (ROS) is an activity normally associated with phagocytic leucocytes, which employ an enzymatic complex, the NADPH oxidase, to catalyze the univalent reduction of molecular oxygen to superoxide. However, it is now apparent that many other cell types, including mammalian spermatozoa, generate ROS. ROS have been implicated in peroxidative damage associated male sub-fertility, and also more recently, in the regulation of normal sperm function. With the obvious biological importance of ROS generation by spermatozoa in mind, the aims of this PhD have been to identify and characterize the mechanisms, and cellular components involved in the generation of ROS by these cells. Experiments investigating ROS generation by human spermatozoa have shown that the mechanisms involved are functionally similar to those pertaining to the NADPH oxidase of phagocytic leucocytes. ROS generation by human spermatozoa is enzymatic in nature and utilizes NADPH as the electron donor, reducing molecular oxygen to superoxide, which subsequently dismutates to hydrogen peroxide. Further similarities with the NADPH oxidase include the probable involvement of a flavoprotein and a role for protein phosphorylation, as regulated by PKC and protein phosphatases. Biochemical and molecular analyses of human spermatozoa have shown that the cellular components that form the NADPH oxidase of phagocytic leucocytes are not present in the spermatozoon. Spectral analyses of human sperm membranes failed to reveal the presence of the characteristic low potential cytochrome b558, and similarly, western blot analyses of human spermatozoa failed to detect the cytochrome b558 or the presence of the two NADPH oxidase cytosolic components, p47phox and p67phox. ROS generating activity was extracted from human spermatozoa, using the non-ionic detergent n-octyl-β-D-thioglucoside. The solubilized protein extract was resolved by non-denaturing PAGE and shown to contain 6 bands with ROS generating activity. ROS generating activity was then isolated in an active form via 2'-5'ADP affinity chromatography. The individual components of this activity were subsequently separated via SDS-PAGE, which revealed a heterogeneous protein population. One of these proteins was purified, and a polyclonal antibody raised against it.
22
Arellanes, Chuautemoc. "Measurements of reactive oxygen species in the particle phase." Diss., Restricted to subscribing institutions, 2008. http://proquest.umi.com/pqdweb?did=1679290751&sid=1&Fmt=2&clientId=1564&RQT=309&VName=PQD.
Full text
23
Sun, Zhenning, and 孫振宁. "Studies on fluorescent probes for the specific detection of reactive oxygen species and reactive nitrogen species in living cells." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B38677490.
Full text
24
Mallon, P. T. "The modulation of experimental colitis by reactive oxygen species scavengers." Thesis, Queen's University Belfast, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.484983.
Full textAbstract:
Inflammatory bowel disease is a common condition causing debilitating symptoms. Existing treatments are successful in many cases but there are a significant proportion of patients in whom conventional therapy fails or results in significant side effects. Alternative treatments are therefore being sought. Reactive oxygen species have been implicated in the pathogenesis of human IBO and experimental colitis. Edaravone and mesna are drugs which have been licenced for use in clinical practice for conditions other than IBO. Edaravone is a potent scavenger of reactive oxygen species such as the hydroxyl ion. It has been shown to reduce long term disability in patients with acute cerebral infarction. It is known that free radicals play an important role in the pathogenesis of secondary brain injury following cerebral infarction. Mesna is licenced for use in the prevention of haemorrhagic cystitis induced by cyclophosphamide chemotherapy protocols. Mesna has been shown to be a scavenger of hydroxyl and hypochlorus free radicals. Mesna, when administered topically has reduced the severity of experimental colitis in TNBS rats. The aim of the experiments in this thesis was to determine the effectiveness of edaravone and mesna at suppressing experimental colitis This thesis had demonstrated that edaravone is effective at suppressing experimental colitis when administered prophylactically. It has a partial benefit in established colitis. Mesna however, when administered orally appears to have no impact on experimental colitis. Edaravone may have a role to playas an alternative therapy for lBO, further trials are however needed to prove its efficacy in patients with IBD.
25
Sand, Carsten. "Pharmacological investigations on reactive oxygen species in the cardiovascular system." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2002. http://dare.uva.nl/document/64883.
Full text
26
Edmonds, Sally Elizabeth. "Hypoxia and reactive oxygen species : therapeutic implications for rheumatoid synovitis." Thesis, Queen Mary, University of London, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.286596.
Full text
27
Rahman, Mashrur. "Reactive oxygen species mediated regulation of autophagy in skeletal muscles." Thesis, McGill University, 2014. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=121322.
Full textAbstract:
Skeletal muscles comprise of approximately 50% of the human body mass and are critical organs for enabling locomotion and exerting metabolic control. Autophagy, a lysosome-dependant catabolic process involved in the degradation of long-lived proteins and organelles, is an important process responsible for maintaining muscle homeostasis. Reactive Oxygen Species (ROS) has been shown to induce autophagy in many different cell types. In this study, we evaluate the effects of physiological levels of mitochondrial-derived reactive oxygen species (ROS) on skeletal muscle autophagy. In differentiated C2C12 myotubes, basal level autophagy and autophagy triggered by 1.5 to 4 hr of acute nutrient deprivation, inhibition of mTORC1, or leucine deprivation were quantified using a long-lived protein degradation assay (index of proteolysis), LC3B autophagic flux, and mRNA expressions of autophagy-related genes. Pre-incubation with antioxidants tempol (SOD mimetic) or N-acetyl cysteine (NAC) significantly attenuates rates of proteolysis and LC3B flux and blocks increases in acute and nutrient deprivation-, rapamycin treatment- and leucine deprivation-triggered autophagy. Similar results were obtained with mitochondira- specific antioxidants mito-tempol and SS31. MitoSOXTM Red fluorescence measurements confirm that mitochondrial ROS levels increase substantially in response to acute nutrient deprivation and rapamycin treatment and that tempol and mito-tempol attenuates this response. Antioxidants decrease AMPK phosphorylation by 40% and significantly augment AKT phosphorylation, but exert no effects on mTORC1-dependant ULK1 phosphorylation on Ser555. Treatment of mice with NAC significantly attenuated basal LC3B autophagic flux in the diaphragm, confirming that endogenous ROS promotes in vivo muscle autophagy. We report for the first time that mitochondrial-derived ROS promote skeletal muscle autophagy and that this effect is mediated in part through AKT inhibition and autophagy initiation via AMPK activation.Les muscles squelettiques constituent environ 50% de la masse du corps humain et représente un organe essentiel permettant la locomotion et le contrôle métabolique. L'autophagie, un processus catabolique lysosome-dépendant, est impliquée dans la dégradation des protéines et des organites à long terme. Elle représente un processus important pour le maintien de l'homéostasie du muscle. Par ailleurs, il a été montré que les radicaux libres (ROS) principalement générés par les mitochondries, induisent l'autophagie dans de nombreux types cellulaires. Dans cette étude, nous voulons évaluer des radicaux libres mitochondriaux (ROS) à un niveau physiologique sur l'autophagie dans le muscle squelettiqueDans les myotubes différenciés C2C12, le niveau basal de l'autophagie et son activation (déclenchées par 1,5 à 4 h de carence aigüe en nutriments, par l'inhibition de mTORC1, ou encore par la privation en leucine) ont été quantifiés à l'aide d'un test de longue durée de dégradation des protéines (indice de protéolyse), par le flux d'autophagie LC3B, ou par les l'ARNm des gènes liés à l'autophagie. La pré-incubation avec des antioxydants de type tempol (SOD mimétique) ou N-acétylcystéine (NAC) atténue considérablement les niveaux de protéolyse, de flux de LC3B et bloque l'activation de l'autophagie secondaire à la carence en nutriments –traitement par rapamycine- ou la carence en leucine. Des résultats similaires ont été obtenus avec es antioxydants spécifiques de la mitochondrie mito-tempol et SS31. Des mesures de fluorescence rouge MitoSOXTM confirment que le niveau de radicaux libres mitochondriaux augmentent considérablement en réponse à une carence en nutriments aiguë ou au traitement par rapamycine et que le tempol et mito-tempol atténue cette réponse. Les antioxydants entraîne une diminution de 40% de la phosphorylation de l'AMPK et augmente significativement la phosphorylation de l'AKT, mais sans exercer aucun effet sur mTORC1 qui est dépendant de la phosphorylation sur Ser555 ULK1. Le traitement des souris avec NAC atténue significativement le flux autophagique basal de LC3B dans le diaphragme, ce qui confirme que les ROS endogènes favorise l'autophagie musculaire in vivo.Nous rapportons pour la première fois que les ROS mitochondriaux sont responsable de l'activation de l'autophagie dans le muscle squelettique et que cet effet est médié en partie par l'inhibition de AKT et de l'initiation de l'autophagie par activation de l'AMPK.
28
Wolfe, James T. "A role for reactive oxygen species in apoptotic cell death." Thesis, University of Leicester, 1996. http://hdl.handle.net/2381/34277.
Full textAbstract:
Apoptosis is a well studied mechanism of controllable cell death, implicated in various disease states. Among other features, it can be characterised morphologically by cell shrinkage, nucleolar disintegration, chromatin condensation and membrane blebbing. Biochemically, apoptotic cell death is most commonly characterised by DNA fragmentation. Originally, it was thought that the cleavage of chromatin between nucleosomes was the biochemical hallmark of apoptosis. More recently it has been shown that the formation of large DNA fragments (30 kilobase-pairs) occurs in the absence of and as a precursor to internucleosomal cleavage. It has also been suggested that reactive oxygen species may play a role in the control of apoptosis. However, conflicting data has been accumulated regarding this role. In this thesis two aspects of apoptosis were studied. Firstly, a technique of labelling DNA termini, caused by strand breakage, was used to detect apoptotic cells. Cells possessing the larger DNA fragments, without concomitant internucleosomal cleavage, were labelled, demonstrating the ability of the technique to detect apoptotic cell death prior to the formation of oligonucleosomal fragments. Secondly, various metal ion chelators and other agents which decrease the formation of intracellular reactive oxygen species were used to modulate apoptosis in a human leukaemic cell line and in primary rat thymocytes. It was found that although some features of apoptosis could be inhibited, others were not. In addition, it was also demonstrated that a redox-active transcription factor, NFkB, thought to be a general modulator of apoptotic cell death, is neither required nor sufficient for apoptosis. This lead to the conclusion that reactive oxygen species are not involved in a common pathway of apoptosis.
29
Perkins, Talayia Nayette. "The effect of reactive oxygen species on aged skeletal muscle." Thesis, Virginia Tech, 1997. http://hdl.handle.net/10919/46503.
Full textAbstract:
The production of reactive oxygen species (ROS) may be a contributor to the progression of sarcopenia. Sarcopenia is a generic term for the loss of skeletal muscle mass, quality and strength. ROS are usually produced by radiation, but are also the byproducts of aerobic metabolism. ROS have been found to mediate various pathological conditions in a variety of tissues, to cause oxidative damage to DNA, proteins, and lipids with advancing age, and is presumably a major factor contributing to changes associated with aging. The purpose of this investigation was to determine whether the sarcoplasmic reticulum (SR) of muscle from aged animals are more susceptible to the deleterious effects of ROS. Using isolated gastrocnemius SR vesicles extracted from adult (12m) and aged (27m) male Brown Norway-Fischer 344 hybrid rats, Ca2+ uptake and release measurements were obtained. The data showed that there was a 33% difference between aged and adult gastrocnemius mass. When gastrocnemius mass was corrected for body mass, the differences was ~20% between the two groups. A 20% decrease in SR Ca2+ uptake rate was noted in aged animals. HOCl also, decreased uptake by similar extents in both groups. This result suggest that the Ca2+ pump's response to ROS are similar in both groups. AgNO3 -induced and H2O2 -induced release in aged animals was 17.94 and 7.39 nmol/mg/min and in adult animals was 30.46 and 7.18 nmol/mg/min, respectively. H2O2-induced release, when expressed as a percent of AgNO3-induced release was increased in aged animals by 54%. The results suggest that the release channel of aged muscle appears to be more sensitive to ROS. In conclusion, the data support the theory that aged animal skeletal muscle is more susceptible to the adverse effects of ROS.Master of Science
30
Zhu, Haizhou. "Novel Reactive Oxygen Species Activated Scaffold from Mechanism to Application." University of Cincinnati / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1573811146199126.
Full text
31
Li, 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 textAbstract:
PharmacologyPh.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
32
Al-Nu'airat, Jomana. "Implications of reactive oxygen species (ROS) in initiating chemical reactions." Thesis, Al-Nu'airat, Jomana (2018) Implications of reactive oxygen species (ROS) in initiating chemical reactions. PhD thesis, Murdoch University, 2018. https://researchrepository.murdoch.edu.au/id/eprint/42916/.
Full textAbstract:
This thesis presents a series of scientific studies exploring the initiation of various chemical reactions with reactive oxygen species (ROS), mainly singlet oxygen. These studies have revealed new mechanistic insights in environmental, industrial and biological systems, have described the associated set of reactions, have illustrated the detection of new radicals i.e., environmentally persistent free radicals (EPFR), and have provided a new insight explaining the spontaneous fire in coal mines. Comprehensive experimental and quantum-mechanical calculations afforded the investigation of oxidation reactions of singlet oxygen with wastewater organic contaminants, for example, the photodegradation of Phenol and Aniline in water. Detailed experimental studies on modelled surrogates, i.e., Anisole, resolved the fundamentals of thermal interaction of coal with iron oxide Fe2O3 nanoparticles. Along the same line of interest, enhancing the combustion efficiency of fuel constitutes a mainstream strategy in the pursuit of meeting the ever-increasing energy demand. Therefore, this thesis also provides a comprehensive mechanistic and thermo-kinetic accounts underpinning the reaction of fuel surrogates, namely Toluene, with singlet oxygen in the internal combustion (IC) engines. Finally, this work extends insights into biological systems, mapping the Alloxan-Glutathione redox cycle to expose the formation of ROS, species that eventually cause necrosis of the pancreatic insulin-producing beta cells and prompt the insulin-dependent diabetes mellitus (IDDM).
The methodology involve customised LED-photoreactors, thermal packed-bed reactor, and various reaction product-monitoring systems, e.g., Fourier transform infrared spectroscopy (FTIR) to quantitate the ignition temperatures of fuel surrogates, in-situ electron paramagnetic resonance (EPR) to elucidate the formation of environmentally-persistent free radicals (EPFR) as well as intermediate radical species, diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) to monitor the chemisorption of organic substrates on the nanoparticles, X-ray diffraction for particles characterisation, as well as broad-scan UV-Vis spectroscopy and high-performance liquid chromatography (HPLC) to identify and quantify the intermediate and product species in solutions.
Results obtained in this thesis elucidate, for the very first time, the formation of para-semibenzoquinone anion (PSBQ) supporting the reaction pathway leading to the formation of para-benzoquinone during the reaction of phenol (and aniline) with singlet oxygen. These results have practical application to quantify the degradation of organic pollutants in wastewater. Investigations regarding combustion applications shows that the presence of singlet oxygen considerably lowers the activation energy of the initiation channels of aromatic hydrocarbons (e.g., in IC engines), resulting in an energetically improved combustion process, the relative reactivity of singlet oxygen, based on the reaction rate constants, follows the order of OH > H > CH3 > 1O2 > HO2 > 3O2. Furthermore, the chemisorption of anisole on α-Fe2O3 surfaces has been elucidated to follow a direct dissociation of the O–CH3 (and OCH2–H), leading to the formation of surface-bound phenoxy radicals and gaseous species at temperatures as low as 25 °C. This insight applies to free-radical chain reactions that induce spontaneous fires of coal, as low-ranked coal comprises ferric oxide nanoparticles, and equally, to coexistence of aromatic fuels with thermodynamically reactive Fe2O3 surface, e.g., in fly ash, at the cooled-down tail of combustion stacks. Results from alloxan-glutathione redox cycle clarified, for the first time, the direct synchronised generation of dialuric acid radical (DA˙) and glutathione radical (GS˙), assigning the nature of the mysterious “compound 305” to the DA˙- GS˙ complex. These results explain the alloxan-induced diabetes on precise molecular bases.
This thesis provides new perspectives on opportunities in understanding the influence of ROS, mainly singlet oxygen (1O2) and superoxide (O2−) in germane chemical reactions. Such attempts will advance the existing ROS-related technologies, and improve the fundamental theories in supports of environmental management and application decisions.
33
Winkler, Jonathan Alexander. "Improving antibiotic activity by manipulating bacterial reactive oxygen species metabolism." Thesis, Boston University, 2012. https://hdl.handle.net/2144/12675.
Full textAbstract:
Thesis (Ph.D.)--Boston University
PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you.The discovery of antibiotics was one of the most important medical breakthroughs of the twentieth century, having a broad impact on overall life expectancy and public health. Unfortunately, antibiotic discovery has slowed significantly in recent times and has failed to match the rising incidence of antibiotic-resistant pathogens. Gram-negative pathogens are a particularly troublesome threat, primarily because these bacteria possess an outer membrane that prevents many antibiotics from accessing their primary cellular targets. While the discovery of novel antibiotics could help to address these issues, alternative strategies, such as improving the activity of preexisting antibiotics, are also needed. Bactericidal antibiotics have recently been shown to share a common mechanism of cell death, despite having different primary, cellular targets. This shared mechanism involves the metabolic production of reactive oxygen species (ROS), which can damage proteins, lipids, and nucleic acids, and can ultimately result in bacterial cell death. The body of work described here shows that this common mechanism can be exploited to improve antibiotic activity, regardless of the antibiotic's primary mode of action. First, I will describe how bacterial metabolism can be predictably perturbed to increase endogenous ROS production, and that increasing endogenous ROS is sufficient to enhance bacterial sensitivity to treatments with ROS-generating biocides, antibiotics, and immune cell attack. I will then describe work indicating that an ancient antimicrobial agent, silver salts, can also increase endogenous ROS production and potentiate the activity of multiple antibiotic classes. Furthermore, I show that silver salts can increase the outer membrane permeability of a Gram-negative organism. This property is exploited to enable vancomycin, an antibiotic that is specific for Gram-positive bacteria, to work against a Gram-negative organism. Together, this body of work demonstrates that bacterial ROS metabolism can be exploited effectively to enhance. antibiotic activity, which ultimately could result in the discovery and development of novel antimicrobial agents.
34
Hecht, castro medeiros Fabio. "The role of reactive oxygen species in thyroid radio-carcinogenesis." Thesis, Université Paris-Saclay (ComUE), 2018. http://www.theses.fr/2018SACLS085.
Full textAbstract:
Les cancers papillaires de la thyroïde (PTC) sont les tumeurs endocrines les plus courantes et représentent 2-3% de tous les cancers humains. Les altérations génétiques les plus pertinentes trouvées dans ces tumeurs sont des mutations dans les gènes BRAF et RAS, et des translocations du gène RET. Ces translocations oncogéniques, connues sous le nom de RET/PTC, résultent de la fusion de RET avec des gènes partenaires non-apparentés. L’exposition aux radiations ionisantes est le facteur de risque le plus important pour la formation de RET/PTC. Durant ces dernières années, notre groupe a mis en évidence un rôle crucial des espèces réactives de l'oxygène (ROS) dans la formation de RET/PTC dans des cellules thyroïdiennes in vitro et a notamment montré que l'irradiation (IR) induit l’établissement d’un stress oxydatif persistant du aux ROS produites par la NADPH Oxydase DUOX1, laquelle est induite à post-IR. Cela conduit à des dommages à l'ADN. Les enfants présentent un risque significativement plus élevé de développer des cancers radio-induits de la thyroïde exprimant RET/PTC, probablement en raison du taux de prolifération élevé des cellules. Ceci suggère que la dynamique de réplication pourrait être impliquée dans la formation de la translocation RET/PTC1. En effet, il a été montré que l'induction pharmacologique d’un stress réplicatif peut favoriser la formation de RET/PTC in vitro dans les cellules thyroïdiennes. Ainsi, pour déterminer si un stress réplicatif peut contribuer aux effets à long terme de l'irradiation: à savoir une persistance des lésions de l'ADN et la formation de RET/PTC1, nous avons analysé les effets à post-IR dans les cellules NTHY-ori3.1. Nos résultats confirment qu’une irradiation des cellules aux rayons X à la dose de 5 Gy induit deux vagues de stress oxydatif: une première vague forte mais transitoire qui se produit dans les minutes qui suivent l'irradiation et une deuxième vague dont l’ augmentation débute 2 jours après l'irradiation pour persister ensuite. Ces deux pics de stress oxydatif conduisent à deux pics de dommages à l'ADN. L'irradiation des cellules à cette dose n’a aucun effet sur la prolifération et sur la progression du cycle cellulaire. Cependant, plusieurs marqueurs de stress réplicatif sont exprimés trois jours après l'irradiation. Par ailleurs, l'analyse de la dynamique de réplication révèle une diminution de la vitesse de réplication à post-IR qui est contrecarrée par les antioxydants, suggérant qu’un stress oxydatif peut contribuer à un stress réplicatif. Enfin, par ChIP-QPCR, nous observons que les gènes impliqués dans RET/PTC1 présentent plus de cassures double brin que des gènes endogènes, et ce, trois jours après l'irradiation. Ainsi, nous proposons qu’un stress réplicatif induit par un stress oxydatif pourrait être potentiellement impliqué dans l'étiologie des tumeurs RET/PTC-positivesPapillary thyroid cancers (PTC) are the most common endocrine tumors and account for 2-3% of all human cancers. The most relevant genetic alterations found in these tumors are mutations in the genes BRAF and RAS, and chromosomal translocations in RET, a proto-oncogene activated in 15-20% of PTCs. These oncogenic translocations, known as RET/PTCs, result from the fusion of RET with unrelated partner genes. Ionizing radiation is a major risk factor for RET/PTC formation, however, the molecular mechanisms involved in these radioinduced translocations just begun to be unveiled. In the past few years, our group has reported a critical role for reactive oxygen species (ROS) in the formation of RET/PTC in thyroid cells in vitro and has also shown that irradiation can elicit a persistent oxidative stress caused by the upregulation of the NADPH Oxidase DUOX1 that leads to DNA damage, mediating at least part of the effects of radiation. However, how could ROS lead to the formation of RET/PTC is not fully understood. Children are at significantly higher risk of developing radio-induced thyroid tumors, specially RET/PTC positive, probably due to the intense proliferation rate of their follicular thyroid cells. This epidemiological observation prompts the assumption that replication dynamics may be involved in RET/PTC formation. Indeed, it has been shown that the pharmacological induction of replicative stress can stimulate the in vitro formation of RET/PTC in thyroid cells. Thus, to investigate whether replicative stress might contribute for the long-term effects of irradiation on DNA damage and RET/PTC formation, we analyzed the effects of radiation in NTHY-ori3.1 thyroid cell lineage in terms of oxidative and replicative stress and replication dynamics. Our results confirm that irradiation triggers two waves of oxidative stress: first, a strong but transient oxidative burst takes place minutes after irradiation and next, a persistently increased oxidative stress that starts only 2 days after irradiation. These two peaks of oxidative stress lead to two peaks of DNA damage. Irradiation caused little or no effect on proliferation nor on cell cycle progression. However, several protein markers of replicative stress, such as pATR, pATM, pChk1 and pRPA are induced three days after irradiation. Moreover, replication dynamics analysis revealed a diminished replication speed that has been reversed by antioxidants, suggesting that oxidative stress may contribute to replication defects. Finally, using ChIP-qPCR, we observed that the genes involved in RET/PTC1 translocation present more double-stranded breaks than RET/PTC-unrelated genes 3 days after irradiation. Hence, we propose that replicative stress is potentially involved in the etiology of RET/PTC-positive tumors
HECHT, Fabio. The role of reactive oxygen species in thyroid radio-carcinogenesis. Rio de Janeiro, 2018. Doctoral thesis - Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil and Université Paris-Saclay, Orsay, France, 2018.O câncer papilífero de tireoide é o tumor endócrino mais comum e corresponde a 2-3% de todos os cânceres humanos. As alterações genéticas mais relevantes relacionadas a esse tumor são mutações nos genes BRAF e RAS e translocações do gene RET, um proto-oncogene ativado em 15-20% dos tumores papilíferos. Essas translocações, conhecidas como RET/PTC, resultam da fusão de RET com diversos outros genes. A radiação ionizante é um importante fator de risco para a formação de RET/PTC, no entanto, o mecanismo molecular responsável por essa translocação radioinduzida ainda não foi elucidado. Nos últimos anos, nosso grupo demonstrou um papel crítico exercido pelas espécies reativas de oxigênio na formação de RET/PTC em células tireoidianas in vitro e também mostrou que a irradiação promove um estresse oxidativo persistente causado pelo aumento de expressão da NADPH Oxidase DUOX1, levando à dano ao DNA, mediando assim parte dos efeitos da radiação. No entanto, como o ROS leva à formação de RET/PTC ainda não é compreendido. Crianças possuem um risco significativamente mais alto de desenvolver tumores tireodianos após a irradiação, especialmente RET/PTC positivos, provavelmente em função da intensa proliferação das células tireodianas. Essa associação sugere que a replicação esteja envolvida na formação de RET/PTC. De fato, foi observado que a indução farmacológica de estresse replicativo pode estimular a formação in vitro de RET/PTC em células tireodianas. Portanto, para investigar se o estresse replicativo contribui com os efeitos da irradiação no longo prazo sobre o dano ao DNA e formação de RET/PTC, nós investigamos o papel da radiação sobre o estresse oxidativo e replicativo, além da dinâmica de replicação de linhagem de células tireodianas NTHY-ori 3.1. Nossos resultados confirmam que a irradiação desencadeia duas ondas de estresse oxidativo: primeiramente, um forte, mas transitório pico de espécies reativas de oxigênio é observado minutos após a irradiação, seguido por um novo e persistente pico que só é observado a partir de dois dias após a irradiação. Esses dois picos de estresse oxidativo resultam em dois picos de dano ao DNA. A irradiação causou pouco ou nenhum efeito na proliferação ou na progressão do ciclo celular. No entanto, vários marcadores de estresse replicativo foram observados três dias após a irradiação, como pATR, pATM, pChk1 e pRPA. Além disso, a análise da dinâmica de replicação mostrou uma diminuição na velocidade da replicação que foi revertida por antioxidantes, sugerindo que o estresse oxidativo contribui para distúrbios dos mecanismos replicativos. Por fim, utilizando ChIP-qPCR, nós observamos que os genes envolvidos na translocação RET/PTC possuem mais quebras duplas do que genes endógenos, dias após a irradiação. Portanto, propomos que o estresse replicativo está potencialmente envolvido na etiologia dos tumores RET/PTC positivos
35
Rizzo, Benedetta <1987>. "Role of Reactive Oxygen Species in signalling and oxidative stress." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6966/1/Benedetta_Rizzo_PhD.pdf.
Full textAbstract:
Results reported in this Thesis contribute to the comprehension of the complicated world of “redox biology”.
ROS regulate signalling pathways both in physiological responses and in pathogenesis and progression of diseases. In cancer cells, the increase in ROS generation from metabolic abnormalities and oncogenic signalling may trigger a redox adaptation response, leading to an up-regulation of antioxidant capacity in order to maintain the ROS level below the toxic threshold. Thus, cancer cells would be more dependent on the antioxidant system and more vulnerable to further oxidative stress induced by exogenous ROS-generating agents or compounds that inhibit the antioxidant system. Results here reported indicate that the development of new drugs targeting specific Nox isoforms, responsible for intracellular ROS generation, or AQP isoforms, involved in the transport of extracellular H2O2 toward intracellular targets, might be an interesting novel anti-leukaemia strategy.
Furthermore, also the use of CSD peptide, which simulate the VEGFR-2 segregation into caveolae in the inactive form, might be a strategy to stop the cellular response to VEGF signalling.
As above stated, in the understanding of the redox biology, it is also important to identify and distinguish the molecular effectors that maintain normal biological and physiological responses, such as agents that stimulate our adaptation systems and elevate our endogenous antioxidant defences or other protective systems. Data here reported indicate that the nutraceutical compound sulforaphane and the Klotho protein are able to stimulate the HO-1 and Prx-1 expression, as well as the GSH levels, confirming their antioxidant and protective role.
Finally, results here reported demonstrated that Stevia extracts are involved in insulin regulated glucose metabolism, suggesting that the use of these compounds goes beyond their sweetening power and may also offer therapeutic benefits hence improving the quality of life.
36
Rizzo, Benedetta <1987>. "Role of Reactive Oxygen Species in signalling and oxidative stress." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2015. http://amsdottorato.unibo.it/6966/.
Full textAbstract:
Results reported in this Thesis contribute to the comprehension of the complicated world of “redox biology”.
ROS regulate signalling pathways both in physiological responses and in pathogenesis and progression of diseases. In cancer cells, the increase in ROS generation from metabolic abnormalities and oncogenic signalling may trigger a redox adaptation response, leading to an up-regulation of antioxidant capacity in order to maintain the ROS level below the toxic threshold. Thus, cancer cells would be more dependent on the antioxidant system and more vulnerable to further oxidative stress induced by exogenous ROS-generating agents or compounds that inhibit the antioxidant system. Results here reported indicate that the development of new drugs targeting specific Nox isoforms, responsible for intracellular ROS generation, or AQP isoforms, involved in the transport of extracellular H2O2 toward intracellular targets, might be an interesting novel anti-leukaemia strategy.
Furthermore, also the use of CSD peptide, which simulate the VEGFR-2 segregation into caveolae in the inactive form, might be a strategy to stop the cellular response to VEGF signalling.
As above stated, in the understanding of the redox biology, it is also important to identify and distinguish the molecular effectors that maintain normal biological and physiological responses, such as agents that stimulate our adaptation systems and elevate our endogenous antioxidant defences or other protective systems. Data here reported indicate that the nutraceutical compound sulforaphane and the Klotho protein are able to stimulate the HO-1 and Prx-1 expression, as well as the GSH levels, confirming their antioxidant and protective role.
Finally, results here reported demonstrated that Stevia extracts are involved in insulin regulated glucose metabolism, suggesting that the use of these compounds goes beyond their sweetening power and may also offer therapeutic benefits hence improving the quality of life.
37
King, Caitriona Maria. "An investigation of antioxidant status DNA repair capability and mutation as a function of age in humans." Thesis, University of Ulster, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390064.
Full text
38
Li, Jian-Mei. "Molecular structure and biochemical properties of an endothelial cell NADP oxidase." Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.272282.
Full text
39
Kafentzi, Maria Chrysanthi. "Reactive copper-oxygen species for C-H activation : influence of nuclearity and oxygen atom donor." Thesis, Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4355/document.
Full textAbstract:
Les monooxygénases à cuivre sont des systèmes enzymatiques capables de transférer un atome d'oxygène à leur substrat de manière hautement régio et stéréo-spécifique. Les complexes modèles de monooxygénases à cuivre ont fourni de précieuses informations sur la structure et la réactivité des espèces «cuivre-dioxygène» impliquées dans une telle réactivité. Cependant, la découverte récente de deux nouveaux systèmes enzymatiques (LPMO et pMMO) capables d'effectuer l'activation des liaisons C-H très énergétiques a réouvert le débat sur les espèces cuivre--oxygène capables d'une telle réactivité. Dans ce travail, nous avons choisi de préparer des complexes bio-inspirés de Cu(I) et Cu(II) avec un ligand contenant un substrat interne. Ces complexes ont été exposés à différents oxydants ou donneurs d'atome d'oxygène et nous avons étudié la régio- et stéréo-sélectivité de la réaction d'oxydation du substrat interne. De plus, nous avons évalue la capacité de ces systèmes à utiliser l'eau comme donneur d'atome d'oxygène. Pour cela, nous avons l'oxydation ou l'activation de l'eau par voie électrochimique afin de générer des intermédiaires cuivre-oxygène conduisant éventuellement à la production de dioxygène ou à l'oxydation sélective du ligand. Enfin, nous nous sommes intéressés aux propriétés d'espèces hétérobimétalliques à haute valence. Par conséquent, deux nouveaux complexes hétérobimétalliques à haute valence contenant du nickel et du cuivre ont été synthétisés. Nous avons étudié leurs propriétés électroniques et leur réactivité envers des substrats externes et internes (ligands) a été évaluée et comparée à la réactivité de leurs homologues homobimétalliquesCopper-containing monooxygenases are enzymatic systems capable of transferring an oxygen atom to their subtrates in highly regio or stereo-specific modes. Model complexes for copper-containing monooxygenases have provided valuable information on the structure and reactivity of several copper-dioxygen adducts. However, the recent discovery of two new enzymatic systems (LPMO and pMMO) able to perform activation of very strong C-H bonds has re-opened the debate on the catalytically relevant copper-dioxygen species. The use of model systems that mimic an enzyme is a simple approach to obtain a better knowledge of how nature works. For this study, Cu(I) and Cu(II) complexes containing ligand-substrate were prepared. After reaction with different oxidants or O-atom donors, we investigated the regio- and stereo-selectivity of the oxidation of the internal substrate. Based on the relatively well-known chemistry of Cu(I) with dioxygen, we, were also interested in investigating the water as an O-atom donor in C-H bond activation reactions. We have therefore investigated electrochemical water oxidation or activation to generate dioxygen and selective oxygen-insertion into the substrate-bound moiety. Finally, we explored the properties of mixed-metal dioxygen species as compared to their homometalic counter-parts. Indeed heterobimetallic active sites are found in various metalloenzymes such as cytochrome c oxidase. Therefore, two new high-valent Cu-Ni heterobimetallic complexes were synthesized. We investigated their electronic properties using various spectroscopic methods and their reactivity was evaluated towards external and internal substrates (indane)
40
Kafentzi, Maria Chrysanthi. "Reactive copper-oxygen species for C-H activation : influence of nuclearity and oxygen atom donor." Electronic Thesis or Diss., Aix-Marseille, 2016. http://www.theses.fr/2016AIXM4355.
Full textAbstract:
Les monooxygénases à cuivre sont des systèmes enzymatiques capables de transférer un atome d'oxygène à leur substrat de manière hautement régio et stéréo-spécifique. Les complexes modèles de monooxygénases à cuivre ont fourni de précieuses informations sur la structure et la réactivité des espèces «cuivre-dioxygène» impliquées dans une telle réactivité. Cependant, la découverte récente de deux nouveaux systèmes enzymatiques (LPMO et pMMO) capables d'effectuer l'activation des liaisons C-H très énergétiques a réouvert le débat sur les espèces cuivre--oxygène capables d'une telle réactivité. Dans ce travail, nous avons choisi de préparer des complexes bio-inspirés de Cu(I) et Cu(II) avec un ligand contenant un substrat interne. Ces complexes ont été exposés à différents oxydants ou donneurs d'atome d'oxygène et nous avons étudié la régio- et stéréo-sélectivité de la réaction d'oxydation du substrat interne. De plus, nous avons évalue la capacité de ces systèmes à utiliser l'eau comme donneur d'atome d'oxygène. Pour cela, nous avons l'oxydation ou l'activation de l'eau par voie électrochimique afin de générer des intermédiaires cuivre-oxygène conduisant éventuellement à la production de dioxygène ou à l'oxydation sélective du ligand. Enfin, nous nous sommes intéressés aux propriétés d'espèces hétérobimétalliques à haute valence. Par conséquent, deux nouveaux complexes hétérobimétalliques à haute valence contenant du nickel et du cuivre ont été synthétisés. Nous avons étudié leurs propriétés électroniques et leur réactivité envers des substrats externes et internes (ligands) a été évaluée et comparée à la réactivité de leurs homologues homobimétalliquesCopper-containing monooxygenases are enzymatic systems capable of transferring an oxygen atom to their subtrates in highly regio or stereo-specific modes. Model complexes for copper-containing monooxygenases have provided valuable information on the structure and reactivity of several copper-dioxygen adducts. However, the recent discovery of two new enzymatic systems (LPMO and pMMO) able to perform activation of very strong C-H bonds has re-opened the debate on the catalytically relevant copper-dioxygen species. The use of model systems that mimic an enzyme is a simple approach to obtain a better knowledge of how nature works. For this study, Cu(I) and Cu(II) complexes containing ligand-substrate were prepared. After reaction with different oxidants or O-atom donors, we investigated the regio- and stereo-selectivity of the oxidation of the internal substrate. Based on the relatively well-known chemistry of Cu(I) with dioxygen, we, were also interested in investigating the water as an O-atom donor in C-H bond activation reactions. We have therefore investigated electrochemical water oxidation or activation to generate dioxygen and selective oxygen-insertion into the substrate-bound moiety. Finally, we explored the properties of mixed-metal dioxygen species as compared to their homometalic counter-parts. Indeed heterobimetallic active sites are found in various metalloenzymes such as cytochrome c oxidase. Therefore, two new high-valent Cu-Ni heterobimetallic complexes were synthesized. We investigated their electronic properties using various spectroscopic methods and their reactivity was evaluated towards external and internal substrates (indane)
41
Jiang, Hong 1964 Dec 6. "Role of reactive oxygen species on mouse sperm hyperactivation and capacitation." Thesis, McGill University, 1994. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=22744.
Full textAbstract:
Capacitation of spermatozoa is essential for fertilization. This process is associated with a change of motility pattern of the spermatozoon called hyperactivation. The possibility that reactive oxygen species play a role in mouse sperm hyperactivation and capacitation was investigated. In this work, we demonstrate that the generation of reactive oxygen species by the reaction xanthine + xanthine oxidase stimulates hyperactivation and capacitation. Reactive oxygen species scavengers such as N-tert-butyl-$ alpha$-phenylnitrone, superoxide dismutase, catalase, dimethysulfoxide, benzoic acid and salicylic acid inhibit basal as well as (X + XO)-induced sperm hyperactivation and capacitation. These results suggest that ${ rm cdot}O sb{2-}$ and H$ sb2$O$ sb2$ react together through the iron catalysed Haber-Weiss reaction to form OH. Investigation of possible $ cdot$OH targets suggest that this radical promotes sperm hyperactivation and capacitation via modification of levels of membrane lipid peroxides and of cellular free -SH groups on small molecules, proteins or both.
42
Díaz, Albíter Héctor Manuel. "Reactive oxygen species and antioxidant enzymes in the Lutzomyia-Leishmania system." Thesis, University of Liverpool, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.569775.
Full textAbstract:
Female phlebotomines are the vectors of Leishmania protozoa. Leishmania reside in the gut of the sand fly and they share this niche with different microbes that interact with either sand fly or Leishmania. Reactive Oxygen Species (ROS) are a major component of the insect innate immune system regulating gut-microbe homeostasis in other insects but the importance of this component in sand flies and its impact on Leishmania is unknown. The sand fly ROS system was initially investigated by examining the expression of antioxidant genes in the midgut of Lu. longipalpis throughout blood digestion using semi-quantitative RT-PCR. Antioxidant genes were differentially expressed throughout digestion and exhibited a peak at 48 h after blood feeding. Catalase was the most upregulated gene. Sand fly fecundity was affected by age and redox balance, as suggested by a significant reduction in egg numbers from older flies as well as after RNAi- mediated silencing of catalase. ROS detoxification appeared to be important during egg development as suggested by the accumulation of catalase in developing oocytes as well as an increase in egg numbers after antioxidant per os supplementation. Sand fly longevity was affected by redox balance, as shown by a significant reduction in survival after RNAi-mediated abrogation of catalase. Dietary addition of antioxidant failed to rescue early mortality, but this group also showed higher levels of phenoloxidase, a potential indicator of bacterial infection. Antioxidant genes were differentially expressed in Leishmania and Serratia colonised guts. Overall, midguts exhibited downregulation of ROS-detoxifying enzymes while Serratia-infected ones displayed the opposite trend. RNAi-silencing of catalase reduced Leishmania populations in the midgut suggesting that oxidative stress is deleterious to this protozoan. Dietary addition of the antioxidant uric acid in Serratia-infected flies increased sand fly mortality as in previous experiments with vitamin C. Although Serratia CFUs were significantly lower in the group with the highest mortality, the population of the resident microbiota was significantly higher in the same group. Interestingly, the numbers of resident microbiota were even higher in flies not infected with Serratia. The implications of the results are discussed in relation to gut immune homeostasis in other insect-microbe systems as well as the possibility of applying some of this information towards understanding the systems governing adult longevity in relation to vectorial capacity and the improvement of sand fly control.
43
Xiong, Yiqin. "ROLE OF REACTIVE OXYGEN SPECIES PEROXYNITRITE IN TRAUMATIC SPINAL CORD INJURY." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/657.
Full textAbstract:
Peroxynitrite (PN, ONOO-), formed by nitric oxide radical (•NO) and superoxide radical (O2•-), plays an important role in post-traumatic oxidative damage. In the early work, we determined the temporal characteristics of PN-derived oxidative damage in a rat spinal cord injury (SCI) model. Our results showed 3-nitrotyrosine (3-NT), a specific marker for PN, rapidly accumulated at early time points (1 hr, 3 hrs), after when it plateaued and the high level was sustained to 1 week post injury. The co-localization of 3-NT and lipid peroxidation derived-4-HNE observed in immunohistochemistry indicates PN is involved in lipid peroxidative as well as protein nitrative damage. PN-oxidative damage exacerbates intracellular Ca2+ overload, which activates Ca2+ dependent calpain-mediated cytoskeletal protein (α-spectrin) degradation. The 145 kD fragments of α-spectrin (SBDP 145), which are specifically generated by calpain, increased dramatically as early as 1 hr after injury although the peak increase did not occur until 72 hrs post injury. The high level waned back toward sham level at one week post injury.
We then carried out experiments to evaluate the beneficial effects of tempol, a scavenger of PN-derived radicals, following SCI. Three pathological events including PN-induced oxidative damage, mitochondrial dysfunction and cytoskeletal degradation were investigated. Immunoblotting and immunohistochemical studies indicated PN-mediated oxidative damage including protein nitration, protein oxidation and lipid peroxidation, were all reduced by a single dose of tempol (300mg/kg, i.p) after SCI. Spinal cord (SC) mitochondrial dysfunction in terms of the respiratory control ratio (RCR) significantly improved by both 150 mg/kg and 300 mg/kg tempol treatments. Moreover, calpain-mediated proteolysis was significantly decreased by tempol, with greater effects on calpain-specific SBDP 145 observed.
Direct PN-scavenging effect of tempol was confirmed in vitro. Exposure of healthy SC mitochondria to SIN-1, a PN donor in vitro, impaired mitochondrial respiration in a dose-dependent manner. Tempol was able to protect mitochondria against SIN-1-induced damage by improving mitochondrial function and decreasing mitochondrial 3-NT formation. These findings strongly support the concept that PN is a crucial player in the secondary damage following SCI. And tempol, by scavenging PN-induced free radicals, provides a promising pharmocotherapeutic strategy for treating acute SCI.
44
Deng, Ying. "ROLE OF THE REACTIVE OXYGEN SPECIES PEROXYNITRITE IN TRAUMATIC BRAIN INJURY." UKnowledge, 2008. http://uknowledge.uky.edu/gradschool_diss/667.
Full textAbstract:
Reactive oxygen species (ROS) is cytotoxic to the cell and is known to contribute to secondary cell death following primary traumatic brain injury (TBI). We described in our study that PN is the main mediator for both lipid peroxidation and protein nitration, and occurred almost immediately after injury. As a downstream factor to oxidative damage, the peak of Ca2+-dependent, calpainmediated cytoskeletal proteolysis preceded that of neurodegeneration, suggesting that calpain-mediated proteolysis is the common pathway leading to neuronal cell death. The time course study clearly elucidated the interrelationship of these cellular changes following TBI, provided window of opportunity for pharmacological intervention.
Furthermore, we conducted a pharmacological study to solidify our hypothesis. First of all, we tested the potency of a membrane permeable, catalytic scavenger of PN-derived free radicals, tempol for its ability to antagonize PN-induced oxidative damage. Tempol successfully inhibited PNinduced protein nitration at dosages of 30, 100 and 300mg/kg. Moreover, early single dose of 300mg/kg was administered and isolated mitochondria were examined for respiratory function and oxidative damage level. Our data showed that tempol reduced mitochondrial oxidative damage, and maintained mitochondrial function within normal limits, which suggested that tempol is efficiently permeable to mitochondrial membrane and mitochondrial oxidative damage is essential to mitochondrial dysfunction. Next, we found that calpainmediated proteolysis is reduced at early treatment with a single dose of tempol. However, the effect of tempol on calpain is short-lived possibly due to systematic elimination. In our multiple dose study, tempol showed a significant inhibitory effect on SBDPs. Consequently, we measured neuordegeneration with the de Olmos aminocupric silver staining method at 7 days post-injury and detected a significant decrease of neuronal cell death.
Together, the time course study and pharmacological study strongly support the hypothesis that PN is the upstream mediator in secondary cell death in the CCI TBI mouse model. Moreover, inhibition of PN-mediated oxidative damage with the antioxidant, tempol, is able to attenuate multiple downstream injury mechanisms. However, targeting PN alone may be clinically impractical due to its limited therapeutic window. This limitation may be overcome in future studies by a combination of multiple therapeutic strategies.
45
Gapper, Catherine Lucia. "Roles and Regulation of Reactive Oxygen Species Involved in Cell Growth." Thesis, University of East Anglia, 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.502509.
Full textAbstract:
The control of the site of growth and subsequent maintenance during expansion are tightly regulated during cellular morphogenesis. Root hairs grow by tip growth, a polarised form of cell growth that is restricted to a single site. Accumulation of ROS produced by RHD2/AtRBOHC at the tip of the growing root hair is required for this tip growth. For ROS to be produced in such a controlled manner, RHD2/AtRBOHC must be well regulated. In this thesis I report two previously undescribed regulatory mechanisms that control RHD2/AtRBOHC activity and localisation within the hair cell. I isolated a mutant, ectopic BPS (eel') that produces ROS ectopically in root hairs: These sites of ectopic ROS accumulation are also sites of growth and the mutant hairs consequently develop abnormal morphology. RHD2/AtRBOHC localisation is altered in this mutant. In wild type RHD2/AtRBOHC is localized at the root hair tip while the protein is distributed throughout the cell in the eel' mutant. This suggests that ECR regulates the localisation of RHD2/AtRBOHC. I mapped the eel' mutation to a 70kb interval at the bottom of chromosome III. Unfortunately sequencing of the 18 genes within this interval did not identify any mutations.
46
Giurnazi, Ali Mansour. "Involvement of reactive oxygen species generation in cellular and subcellular fractions." Thesis, University of Nottingham, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.318298.
Full text
47
D'Souza, Richard Joseph. "The importance of reactive oxygen species in determining mesangial cell growth." Thesis, St George's, University of London, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.283240.
Full text
48
Muzaffar, Saima. "Reactive oxygen species and the pathophysiology of adult respiratory distress syndrome." Thesis, University of Bristol, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.271916.
Full text
49
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 text
50
Todd, Adam. "The role and inhibition of reactive oxygen species (ROS) in psoriasis." Thesis, University of Sunderland, 2009. http://sure.sunderland.ac.uk/3699/.
Full textAbstract:
Psoriasis is a chronic inflammatory skin disorder that affects around two percent of the population. There are many treatments available for the management of psoriasis including topical therapy, systemic agents and phototherapy. Despite the number of treatments available, however, there are still problems in the management of psoriasis. It is suggested here that the thioredoxin enzyme system may play a role in the pathology of psoriasis. Using specific molecular modelling techniques, a lead compound, RDP00060, was identified as a potential inhibitor of thioredoxin reductase, a key enzyme in the thioredoxin system. In vitro RDP00060 showed moderate inhibitory activity against the thioredoxin enzyme system with an IC50 value of 1.4 mM. RDP00060 also showed powerful activity in an MTT assay using a human papilloma virus immortalized keratinocyte (HPV-16) cell line. To increase the inhibitory activity towards thioredoxin reductase, molecular modelling techniques were used to identify analogues of RDP00060 with a high binding affinity for thioredoxin reductase. Several novel compounds were then synthesized, characterized and evaluated for inhibitory activity towards the thioredoxin system. One of the compounds, N-(3,4-bis-(toluene-4- sulfonylamino)phenyl)-2-furamide (33f) showed good inhibitory activity against the thioredoxin enzyme with an IC50 value of 37 μM. It is anticipated that N-(3,4- bis-(toluene-4-sulfonylamino)phenyl)-2-furamide (33f) binds to thioredoxin reductase irreversibly through a 1,4-conjugate addition mechanism. This compound also showed powerful activity in the MTT assay using an HPV-16 immortalized keratinocyte cell line. Further testing revealed that N-(3,4-bis-(toluene-4-sulfonylamino)phenyl)-2- furamide (33f) also showed apoptotic and antiproliferative properties in human Tcells. As a result of this work, N-(3,4-bis-(toluene-4-sulfonylamino)phenyl)-2- furamide (33f) has been selected for further investigation as a potential antipsoriatic agent.