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Effects of chemopreventive compounds on cytochrome P450s
Křížková, Jitka ; Hodek, Petr (advisor) ; Helia, Otto (referee) ; Václavíková, Radka (referee)
CHARLES UNIVERSITY IN PRAGUE Faculty of Science Department of Biochemistry Effects of chemopreventive compounds on cytochrome P450s Summary of Ph.D. Thesis RNDr. Jitka Křížková Supervisor: prof. RNDr. Petr Hodek, CSc. Prague 2010 Introduction 1 Introduction According to the World Health Organization statistics, cancer is one of the leading causes of death in the human population worldwide for more than 50 years. Moreover, colorectal and gastrointestinal tract cancers are one of the main types of cancer leading to overall cancer mortality. Prevention consisting in a healthy lifestyle and a natural diet is suggested to be one of the main approaches to reduce cancer risk. In recent years, the consumption and use of dietary supplements containing concentrated chemopreventive phytochemicals increased dramatically. Flavonoids, as the most popular representatives of chemopreventive compounds, present in foods (fruits, vegetables, herbs, beverages) and dietary supplements have the potential to modulate the activity of xenobiotic-metabolizing enzymes [Hodek et al., 2002]. Among proteins interacting with flavonoids, cytochrome P450s (CYPs), monooxygenases metabolizing xenobiotics (e.g. drugs, carcinogens), play the most prominent role. The two members of CYP1A subfamily, CYP1A1 and CYP1A2, are involved in the...
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Functional assessment of Bcl-2 family proteins in mitochondrial metabolism and beyond
Sovilj, Dana ; Anděra, Ladislav (advisor) ; Mráček, Tomáš (referee) ; Živný, Jan (referee)
(CZ) Od jejich prvotní identifikace v háďátku C. elegans a také v lidských buňkách před více než 30 lety jsou proteiny z rodiny Bcl-2 spojovány s indukcí, regulací a potlačením mitochondriální apoptotické signalizace, ale také se mohou uplatňovat při modulaci neapoptotických signálních dráh. V této studii jsme si stanovili za hlavní cíl rozšířit stávající znalosti o neapoptotických rolích hlavních proapoptotických proteinů z Bcl-2 rodiny, BAX a BAK, zejména pak na jejich roli v buněčném metabolismu. Pomocí genové editace využitím CRISPR/Cas9 jsme eliminovali expresi těchto proteinů v lidských nádorových buňkách různého tkáňového původu a v těchto Bax/Bak- deficitních buňkách jsme primárně analyzovali mitochondriální respiraci a buněčnou glykolýzu. Zatímco eliminace exprese Bax a Bak neměla žádný patrný vliv na glykolýzu ve všech testovaných buněčných liniích, v závislosti na buněčném typu modulovala mitochondriální respiraci. Eliminace exprese Bax a Bak v buňkách rakoviny tlustého střeva HCT-116 neměla vliv na mitochondriální respiraci, ale zjevně ovlivnila mitochondriální respiraci v Bax/Bak-deficitních buňkách odvozených od glioblastomu (U87) a lymfomů (HBL-2, UPF1H, UPF1G). Bax/Bak -/- buňky U87 významně upregulovaly mitochondriální respiraci a akcelerovaly svou proliferaci a také nádorový růst...
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Modulation of mitochondrial transfer by influencing mesenchymal stem cells
Fráňová, Markéta ; Krulová, Magdaléna (advisor) ; Rohlenová, Kateřina (referee)
Mesenchymal stem cells (MSCs) have the ability to modulate the immune response. They use several mechanisms to affect the function of immune cells, and mitochondrial transfer is one of them. Recieving mitochondria from MSCs induces metabolic changes in immune cells, thereby promoting their shift to an anti-inflammatory phenotype. Due to their properties, MSCs have a potencial to be used in therapies, for example in a treatment of autoimmune diseases. The problem of MSCs-based therapies is their low efficacy, mainly due to the high mortality of stem cells after transplantation. In order to achieve at least some effect, the large number of cells is needed for application. The required number of cells can be obtained only by in vitro expansion. However, a long-term culture has a negative impact on MSCs and their immunomodulatory properties. Enhancing MSCs function could increase the efficacy of MSCs-based therapies. The aim of this thesis was to determine whether mitochondrial transfer can be modulated by stimulation of MSCs with selected factors. MSCs were treated with rapamycin, insulin-like growth factor 1 (IGF-1), interferon gamma, or oligomycin. Then the effect of these factors on mitochondria and their transfer to immune cells, metabolism, and immunomodulatory properties of MSCs was analyzed. We...
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Glucose effect on lipid metabolism homestasis in pancreatic β-cells
Stokičová, Linda ; Holendová, Blanka (advisor) ; Horáková, Olga (referee)
Lipids create an essential part of pancreatic β-cells. Not only they are the principal structural components and energy source, but they also play an indispensable role in β-cell physiology. Their metabolism is tightly interconnected with the metabolism of glucose, the fundamental β-cell molecule. The presence of lipids is critical for glucose-stimulated insulin secretion and their turnover is inevitable for correct β-cell function. Lipids in the form of triacylglycerols, retinyl esters and cholesterol esters are stored in lipid droplets. These dynamic cellular structures are important for lipid metabolism and the protection of the cells against various types of stress. However, chronic exposure of β-cells to glucose and lipids can lead to disrupted glycerol/non-esterified fatty acid (GL/NEFA) cycle function, glucolipotoxicity and further dysfunction of β-cells, their dedifferentiation, insulin resistance, and finally type 2 diabetes. The experimental part focused on lipid metabolism in pancreatic β-cells in connection with glucose metabolism and redox environment. Glucose-induced expression of proteins involved in lipid metabolism (fatty acid activation, lipolysis, lipogenesis, etc.) and the effect of modulated redox environment was investigated in β-cell line INS1E and isolated mouse pancreatic...
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The role of glutamine in leukemia cell metabolism
Sitdikova, Karina ; Hložková, Kateřina (advisor) ; Zelenka, Jaroslav (referee)
Leukemia is a heterogeneous group of hematological malignancies that result from the abnormal proliferation of immature blood cells. One of the hallmarks of tumor cells is their altered metabolism. Therefore, therapy targeting deregulated metabolic processes is an attractive strategy for the treatment of malignancies, including hematological ones. Amino acid metabolism is an important part of cellular metabolism, and targeting it appears to be a key attractive strategy in the treatment of leukemia. Glutamine, a conditionally essential amino acid, plays a crucial role in energy metabolism and maintaing the redox balance of leukemia cells, thereby contributing to their growth and proliferation. Strategies to treat leukemia by targeting glutamine metabolism include glutamine depletion, the use of glutamine transporter inhibitors and glutaminase enzyme inhibitors. To ensure the effectiveness of leukemia treatment, it is essential to recognize that glutamine is involved in numerous metabolic pathways, each of which is regulated by multiple factors. As a result, therapies targeting glutamine metabolism should be carefully designed to avoid affecting healthy cells and patient immunity. This thesis describes leukemia, including its types and treatments, and glutamine metabolism and its potential targeting...
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Zinc in food suplements
Sauchanka, Katsiaryna ; Suková, Petra (referee) ; Řezáčová, Veronika (advisor)
The aim of this bachelor thesis was to determine zinc in the dietary supplements by the voltammetric method. The general properties of zinc, its occurrence, toxicity and influence on human health are described in the first part. Next the methods, including a detailed description of the voltammetric analysis, are summarized. The experimental part is focused on the process of optimization of the conditions for zinc voltammetric analysis and the application of the optimised method on real samples.
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Investigation of the effect of creatine in combination with magnesium and vitamin C on the performance of the individual person
Vlasák, Jan ; Němcová, Andrea (referee) ; Diviš, Pavel (advisor)
Creatine is nitrogen-containing organic acid which naturally occurs in the human body. The aim of this work was to determine the optimal dose of creatine in combination with vitamin C and magnesium for male respondents aged 18-26 years. They were divided into two groups differing in the creatine dosage. Group 1 took smaller dose of creatine (3 g per day) and group 2 higher dose of creatine (10 g per day). Both groups took both magnesium and vitamin C at constant doses throughout the study. The effects of significantly different dose of creatine in the individual groups were compared with each other in terms of the performance of individuals in the powerlifting, the anthropological changes and the overal metabolism of the intakes. In all disciplines of powerlifting, group 1 recorded higher average weight gains, which were not found to be statistically significant at a significance level of alpha 0,05. Anthropological changes were measured using the InBody 160 and a diagnostic measuring tape. In both cases, group 1 recorded better results than group 2, but these results were not statistically significant at a significance level of alpha 0,05. The total metabolism of the accepted dietary supplements was investigated through analytical methods. The urine of each respondent was regularly collected and subsequently analyzed during the research. Determination of creatinine, a creatine waste product, was performed by UV-VIS spectrophotometry using the Jaffe reaction. Vitamin C was analyzed by RP-HPLC. Magnesium was determined by the ICP-OES method. After creatine suplemantion of 3 per day, group 1 showed a slight increase in creatinine in the urine, but still in the physiological range. At the significance level alpha 0,05 there was no statistically significant difference. Group 2 showed an increase above the physiological limit which was already a statistically significant difference. Overall, creatine supplementation of 3 g per day has been found as a sufficient intake of creatine needed to build up muscle mass, increase energy metabolism and overall physical performance. The metabolization itself works very well and within the physiological values.
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Metabolic setup of Drosophila macrophages during the immune response
KREJČOVÁ, Gabriela
Adjustment of cellular metabolism is a key function that allows macrophages to fulfill their roles in the body. While the pro-inflammatory polarization of macrophages has been extensively studied in mammalian models, it has not yet been satisfactorily investigated in insects. The study presented in this thesis therefore attempts to elucidate the metabolic setup of macrophages during the immune response in Drosophila melanogaster.
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