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Selected aspects of redox metabolism in leukemogenesis
Myšáková, Michaela ; Pimková, Kristýna (advisor) ; Kuželová, Kateřina (referee)
Blood cancers are caused by the accumulation of mutations in haematopoietic stem cells. This creates a malignant clone that has a selection advantage due to improved survival and unrestricted proliferation, a process of leukaemia development called leukemogenesis. Leukemogenesis is a complex process and it is difficult to identify a single mutation that is responsible for the transformation of haematopoietic cells. In addition to transcriptional deregulation caused by oncogenic fusion proteins, mutations in specific genes that regulate critical signaling pathways play a critical role in leukemogenesis. Examples of such genes include mutations in the isocitrate dehydrogenase 1 and 2 genes (mutIDH1/2). These genes are thought to play an important role in the development of leukaemia, as indicated by their increasing frequency in the progression of myelodysplastic syndrome to acute myeloid leukaemia. The functions of mutIDH1/2 include epigenetic regulation, changes in metabolism and redox homeostasis. It has been shown that regulation of reactive oxygen species (ROS) production and elimination, so-called redox homeostasis, is important for the proper function of haematopoietic stem cells and its disruption is a frequent phenomenon accompanying malignant transformation of these cells. Some mutations,...
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Evaluation of antibiotic-induced mitochondrial superoxide production in adherent cells
Ingrová, Kateřina ; Chmelíková, Larisa (referee) ; Zumberg, Inna (advisor)
The theoretical part of this bachelor´s thesis contains a description of the effect of reactive oxygen species on oxidative stress by mitochondria and the consequences of antibiotics use in cell line culturing. The cell line studied in this bachelor´s thesis is the mesenchymal stem cells (MSCs). The practical part describes the procedure of the experiment including cell culturing, passaging and cell labeling. The proposed experiment was repeated with sufficient number of repetitions. Finally, confocal microscopy images were processed in the MATLAB programming environment.
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Impact of Immunonutrition on the Patients With Cystic Fibrosis
Hloch, Ondřej ; Charvát, Jiří (advisor) ; Kohout, Pavel (referee) ; Rušavý, Zdeněk (referee)
The impact of immunonutrition in patiens with cystic fibrosis Abstract The aim of the study was to evaluate the application of immunonutrition in adults with cystic fibrosis (CF) and malnutrition, who have been receiving enteral nutrition in the form of standard sipping for at least a year. In 30 adult patients, immunonutrice (Impact) was given for 8 weeks. After 8 weeks, patients returned to standard nutritional support. The application of immunonutrition led to a significant reduction in systolic blood pressure and heart rate, to an increase in glomerular filtration and significant changes in the plasma aminoacidogram. Serum amyloid-A (SAA) levels decreased significantly and increased again after the intervention. However, immunonutrition administration was associated with an increase in serum malonyldialdehyde, a decrease in serum glutathione peroxidase and selenium. Thus, administration of immunonutrition led to an increase in oxidative stress, but almost all values remained within physiological limits. At 6-year follow-up, the long- term prognosis in the multivariate analysis depended only on baseline FEV1 and the degree of pulmonary involvement, respectively. The frequency and duration of subsequent hospitalizations and long-term prognosis were significantly associated with plasma fibrinogen levels....
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Use of stress factors for the production of lipid substances by yeasts of the genus Metschnikowia
Tručková, Marie ; Márová, Ivana (referee) ; Němcová, Andrea (advisor)
This Master´s thesis consists of two parts. The theoretical part is focused on the influence of various stress factors in the cultivation process, such as osmotic stress, oxidative stress, dehydration, cultivation time, pH or temperature on yeasts of the Metschnikowia genus. The practical part deals with osmotic and oxidative stress. Oxidative stress was performed under two different conditions (various cultivation time and temperature). The properties of yeast production were monitored mainly by gas chromatography and marginally also by flow cytometry. The analysis was performed for Metschnikowia pulcherrima, Metschnikowia andauensis, Metschnikowia chrysoperlae, Metschnikowia sinensis, Metschnikowia zizyphicola and Metschnikowia shanxiensis strains. The results showed that both oxidative stress and osmotic stress induce better lipids production. The amount of lipids, especially the fatty acid composition, also varied depending on the strains studied and the culture conditions used. The production of unsaturated fatty acids was further demonstrated in this work. The most suitable medium for the production of lipids and unsaturated fatty acids was the salt medium. It is clear that yeasts of the genus Metschnikowia are highly adaptable yeasts. Therefore, they might be potentially auspicious biotechnology producers.
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Oxidative stress biomarkers of the erythrocyte in the newborn - a follow-up study
Zubatá, Karolína ; Čečková, Martina (advisor) ; Hronek, Miloslav (referee)
Charles University University of Porto Faculty of Pharmacy in Hradec Králové Faculty of Pharmacy Department of Pharmacology and Toxicology Department of Biological Sciences Student: Karolína Zubatá Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Consultants: Susana Rocha, Ph.D., prof. Alice Santos-Silva, Ph.D. Title of diploma thesis: Oxidative stress biomarkers of the erythrocyte in the newborn - a follow-up study Increased levels of oxidative stress (OS) have been described in healthy, full-term newborns as a consequence of the drastic changes introduced by birth and by the exposure to extrauterine environment. Our intention was to examine the OS levels in red blood cells (RBCs) of neonates and to further understand the changes that the newborn organism undergoes with its newly- acquired autonomy as this knowledge is limited and there are no reference values. Umbilical cord blood samples were collected from a small population of newborns (n = 8) and several hematological and biochemistry parameters were evaluated. Our experimental data consist of OS biomarkers measurements performed in different fractions of blood (RBC membrane, total RBCs and plasma): membrane bound hemoglobin (MBH), lipid peroxidation (LPO), quantification of catalase (CAT) and glutathione peroxidase (GPx) activities,...
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Myocardial phospholipases A2 and oxidative stress
Závišková, Kristýna ; Míčová, Petra (advisor) ; Chytilová, Anna (referee)
Heart and vascular diseases, in which oxidative stress plays an important role, are the most frequent cause of death in developed countries. Therefore today's researches focus on clarifying signaling pathway and their components that operates in these processes. One of the possible key factors can be phospholipases A2. These enzymes hydrolyze unsaturated fatty acids from C2 position on phospholipids, which easily subject to the oxidative modification due to their double bonds. There are five groups: the secreted, the cytosolic, the calcium independent, the platelet-activating factor acetylhydrolases and the lysosomal phospholipases A2. They differ in the requirement for calcium ions for its activity, molecular weight, position of disulfide bonds and amino acids sequences in the active site. Their main importance is to keep the stability and integrity of cell membranes and produce lipid signaling molecules (free fatty acids, lysophospholipids, eicosanoids). The phospholipases A2 play a dual role during oxidative stress in myocardium. First, they have a positive effect by protecting membranes against oxidative stress due to their higher affinity for removal of peroxidized fatty acids from membrane phospholipids. On the other hand, the phospholipases A2 can also cause destructive effects during...
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The effect of endothelial cell proliferation on susceptibility to mitochondrially controlled apoptosis and oxidative stress.
Blecha, Jan ; Novák, Petr (advisor) ; Plecitá, Lydie (referee)
Mitochondria are multifunctional organelles playing a key role in energy metabolism and cell death induction. Mitochondria, and specifically their respiratory chain, are also the main producers of reactive oxygen species (ROS) in cells. Metabolism can be affected by the state of cellular proliferation and certain ROS-inducing agents have an antiangiogenic effect based on the preferential elimination of proliferating endothelial cells (EC). Therefore, in this work we investigated, whether mitochondria could be responsible for different sensitivity of proliferation and confluent EC to cell death. We mainly focused on systems that regulate ROS level and apoptosis: respiratory chain (ROS production), antioxidant defense (ROS detoxification) and Bcl-2 family of proteins (apoptosis regulation). First, we treated EC with functional and nonfunctional respiratory chain with various oxidative stress- and apoptosis-inducing agents and determined ROS production and susceptibility to apoptosis in proliferating and confluent cells. Our results show that functional respiratory chain greatly increases the susceptibility of proliferating cells to ROS induction and apoptosis, whereas in qiescent cells it protects against cell death. Given these findings, we assessed the activity of respiratory chain in proliferating...
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Antioxidant system in hypoxic heart
Sotáková, Dita ; Žurmanová, Jitka (advisor) ; Kalous, Martin (referee) ; Babula, Petr (referee)
The cardiovascular disease, particularly acute myocardial infarction, is the most common cause of death worldwide. It is well documented that adaptation to chronic hypoxia increases resistance to ischemia-reperfusion (I/R) injury in heart tissue. Reactive oxygen species (ROS) play an important signalling role by the activation of the protective pathways during I/R, although, the excess of ROS during reperfusion leads to cardiac tissue injury. As the cellular antioxidant system is responsible for the maintenance of redox homeostasis, the main aim of this thesis was to investigate the relationship between myocardial tolerance to I/R injury and regulation of main components of antioxidant systems, related transcription factors and their target genes in protective and non- protective regimens of chronic hypoxia. We found differences in cardioprotective phenotype in rats exposed to three regimens of chronic normobaric hypoxia (FiO2 0.1, 3 weeks). The adaptation to continual (CNH) and intermittent (CNH-8; 8 h/day) regimen of hypoxia increased myocardial resistance to I/R damage, whereas 1-hour daily interruption of hypoxic adaptation (INH-23) abolished cardioprotective effect and decreased the ratio of reduced and oxidized glutathione (GSH/GSSG). Both cardioprotective regimens significantly increased...
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Oxidative stress and condition-dependence of ornamental signals of quality in socially monogamous songbird
Valášek, Stanislav ; Tomášek, Oldřich (advisor) ; Sedláček, Ondřej (referee)
6 ABSTRACT Conditional ornaments plays irreplaceable role in sexual selection in non-small part of by sexual reproduction reproducing animals. Fastidiousness of generating and later also carrying of these ornaments which show condition of their wearer, burdens also metabolism in non-small scale. This thesis tests hypothesis of mutual addiction between conditional ornaments, as the indicators of qualities of individuals and metabolism, as the most significant source of free radicals which are responsible for oxidative stress. The real weight of influence of ornament fastidiousness on organism, resp. on redox state, is tested in this thesis. Manipulations which were performed with individual males of model species should point how much the selected factors correlate each other. The barn swallow (Hirundo rustica) is the model species. Analyses of dates collected during trapping which were realized in breeding seasons in 2012 and 2013 does not show any important trends between observing variables. This fact is confirmed by minimal differences and inconsistent variability of levels of measured antioxidants - oxidoreductases, superoxide dismutase and glutathione peroxidase. The marginal effect of manipulations with one of the conditional ornaments which are presented in model species supports the hypothesis of...
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Proteomic analysis of selected oncohematological diseases
Pimková, Kristýna ; Dyr, Jan (advisor) ; Kodíček, Milan (referee) ; Petrák, Jiří (referee)
Oxidative stress is an important factor in carcinogenesis of oncohematological diseases. However its role in the pathogenesis of myelodysplastic syndromes (MDS) remains unclear. In this study, we have determined the oxidative status and evaluated proteomic changes in plasma of MDS patients as a consequence of oxidative dysbalance (oxidative modifications, protein-protein interaction and complex forming). We measured the levels of total cysteine, homocysteine, cysteinyglycine, glutathione, nitrites and nitrates in the plasma from 61 MDS patients and 23 healthy donors using high performance liquid chromatography. Glutathione and nitrites levels reduced significantly while other aminothiols levels increased significantly in plasma of MDS patients. This association with oxidative stress did not correlate with iron overload. We also found enhanced levels of asymmetric dimethylarginine in serums of middle aged patients with MDS that correlate to posttranslational modifications of proteins arginyl residues. Furthermore, carbonylated proteins level was significantly elevated in MDS patients compared to healthy donors. Using mass spectrometry, 5 S-nitrosylated blood platelets proteins were identified in plasma and blood platelets of MDS patients and set of 16 plasma proteins with high probability of...
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