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The role of cholesterol-7alpha-hydroxylase in cholesterolemia regulation
Procházková, Martina ; Kovář, Jan (advisor) ; Zelenka, Jaroslav (referee)
Cholesterol 7α-hydroxylase (CYP7A1) is an enzyme catalyzing the first step of conversion of cholesterol to bile acids. The enzyme activity is regulated to supply enough bile salts necessary for absorption of fats in the intestine. In some species it contributes to cholesterol elimination from the body when dietary cholesterol intake is high and, in such a way, protects against the development of hypercholesterolemia. CYP7A1 activity can be therapeutically affected by administration of bile acid sequestrants that increase the enzyme activity and thus lower cholesterolemia, and also by administration of bile salts. The enzyme deficiency in humans results in hypercholesterolemia. Several single nucleotide polymorphisms were identified in gene encoding CYP7A1 in humans. They form three large haplotype blocks. The most attention has been paid to the -203A>C polymorphism that has an impact on cholesterol and lipoprotein concentrations, on the response of cholesterolemia to dietary intervention and on the response to hypolipidemic drugs. Key words: Bile acids, cholesterol, cholesterol 7α-hydroxylase, diet, genetics, treatment of hypercholesterolemia
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Expression of apoptosome pathway regulators and activation of apoptosome apparatus in non-small cell lung carcinoma
Moravčíková, Erika ; Křepela, Evžen (advisor) ; Kovář, Jan (referee) ; Kotyza, Jaromír (referee)
Background: The apoptosome pathway is interesting as potential therapeutic target because it plays an important role in the cancer chemotherapy- and biological therapy-induced apoptosis as well as in amplifying the death receptor and cytotoxic-granule-induced pathways. The functionality of apoptosome apparatus in non-small cell lung carcinoma (NSCLC) cells and tissues is often impaired due to defects in apoptosome pathway by changes in expression and/or acquired mutations and/or modifications of apoptosome components or its regulators that play a significant role in cancer cell proliferation and treatment unresponsiveness. Therefore, this thesis is aimed at the investigation of the expression status of apoptosome pathway regulators (survivin, HBXIP, XIAP, APIP, and UACA) and of the readiness of apoptosome apparatus activation in non-small cell lung carcinoma cells and tissues. Methods: Following methods were used in this thesis: isolation and quantification of total RNA, real-time RT-PCR analysis, preparation of cell-free cytosol samples and extracts from cells and tissues, gel-filtration chromatography, Western blot analysis, enzyme analyses and cell culture techniques. Results and conclusion: Non-small cell lung carcinoma has a higher predisposition to apoptosome-mediated apoptosis than normal...
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Regulation of lipoprotein lipase activity in circulation
Zemánková, Kateřina ; Kovář, Jan (advisor) ; Vrablík, Michal (referee)
Lipoprotein lipase (LPL) is a key enzyme in lipoprotein metabolism. The enzyme catalyzes hydrolysis of triacylglycerols (TG) of chylomicrons and of very low density lipoproteins (VLDL). However, the mechanisms involved in the regulation of this protein are not fully understood yet. Therefore, the aim of the theses is to study selected aspects of LPL activity regulation. Recently discovered apolipoprotein A-V (apo A-V) substantially affects triglyceridemia and it is presumed that it may function as LPL activator. However, its concentration in the blood is extremely low and we therefore investigated whether most of apo A-V could be bound to the heparan sulfate proteoglycan (HSPG) of vascular wall similarly to LPL. Intravenous heparin application in healthy volunteers resulted in an expected increase in LPL activity but apo A-V concentration did not change. Our results do not support the hypothesis that most of apo A-V is bound to HSPG of the capillary endothelium. An alcohol consumption plays also a role in LPL regulation - the long-term moderate alcohol consumption is known to increase enzyme activity; on the contrary, it is presumed that LPL activity is inhibited immediately after alcohol consumption. However, the direct evidence for such a premise is missing. The other aim of the theses was to...
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Design of system for indication of gas leakage by ultrasonic microphone
Bohuš, Michal ; Kovář, Jan (referee) ; Šotner, Roman (advisor)
The aim of this project is detection of gass leak based on the ultrasound sensing. Work introduces ultrasound, mechanism of its propagation and attenuation. From all of the available microphones, the piezoelectric microphone was chosen. Project continues with description of the device, which can be capable of detection of the ultrasound leakage in dangerous, explosive environment. This type of device must meet requirements of SIL 2 standard and ATEX directive for zone 2. Project discusses LNA (Low Noise Amplifier), filters and detection circuits design. The device is modular what means that each module can be freely replaced. The role of these modules is to convert analog signal to digital form suitable for microcontroller HERCULES TSM57012.
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Gilbert Syndrome.
Šimáková, Eva ; Kuklík, Miloslav (advisor) ; Kovář, Jan (referee)
This thesis focuses on finding a possible link between genotype typical for Gilberts syndrome and specific diseases. It nvestigates a possible protective effect of the 7TA allele. It explains the origin, symptoms, pathology of this syndrome and its consequences for clinical medicine. Possible protective effect of this polymorphic mutation including reduced incidence of vascular diseases (myocardial infarction, stroke, atherosclerosis, etc.). is discussed. Reduced oxidative stress in hyperbilirubinaemia can be the mechanism behind. The work was carried out in the co-operation with the GENVIA laborator.
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Molecular mechanisms of apoptosis induced by photodynamic activation in cancer cells
Moserová, Irena ; Králová, Jarmila (advisor) ; Kuželová, Kateřina (referee) ; Kovář, Jan (referee)
Photodynamic therapy (PDT) is a treatment modality for cancer. It combines selective accumulation of chemical compounds, called photosensitizers (PS), with light to irreversibly damage cancer cells via oxidative stress. The main goal of this thesis was to study photosensitizers represented by a unique group of newly synthesized porphyrin derivatives with glycol chain substitution. Glycol-functionalized porphyrins containing one to four low molecular weight glycol chains that are linked via ether bonds to the meta-phenyl positions of meso-tetraphenylporphyrin (mTPP(EG)1-4) were compared with fluorinated (pTPPF(EG)4) and nonfluorinated (TPP(EG)4) derivatives having glycol chains in para-phenyl positions. The cellular uptake and photodynamic activity was significantly dependent on terminal groups of the glycol substituent. Hydroxy glycol porphyrins, in contrast with methoxy glycol porphyrins, exhibited efficient intracellular transport and high induction of apoptosis in tumor cell lines in vitro. After initial testing effective prototype hydroxy ethylene glycol derivatives were selected and analyzed in detail. Para derivatives pTPP(EG)4 and pTPPF(EG)4 accumulated mainly in lysosomes whereas meta derivatives mTPP(EG)1-4 in the endoplasmic reticulum (ER). Position of ethylene glycol chain on the...
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Role of endocytosis and endosomal acidification in TRAIL-induced apoptosis
Hradilová, Naďa ; Anděra, Ladislav (advisor) ; Kovář, Jan (referee)
TRAIL (TNF-related apoptosis inducing ligand) became known for its ability to selectively eliminate cancer cells. This ligand is a member of the TNF (tumor necrosis factor) ligands family and triggers extrinsic apoptotic pathway by binding of its death receptor 4 or 5 (DR4/5), and subsequent formation of death-inducing signalling complex (DISC). This signalling complex is required for successful transmission of apoptotic signal and activation of proximal caspases. However, regulation of the initial steps leading to activation of caspases is still not fully understood. Endocytosis of a TRAIL- DR4/5-DISC complex can be one of modulators of the initiation of extrinsic apoptotic pathway. Recent studies show controversial data documenting that endocytosis of TRAIL receptosomes can in cell type specific manner either positively or negatively influence TRAIL-induced apoptotic signalling. In this study, we focus on the analysis of a role of endocytosis and acidification of endosomal compartments during TRAIL-induced apoptosis in human colorectal cancer cell lines. Our results support the view that both clathrin-dependent endocytosis of TRAIL receptosome and endosomal acidification positively affect activation of caspases during the early stages of TRAIL-induced apoptosis. Inhibition of endocytosis or endosomal...
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Analysis of attacking playing systems Czech football team U19 on the elite qualification Europe championship
Kovář, Jan ; Frýbort, Pavel (advisor) ; Kokštejn, Jakub (referee)
Title: Analysis of attacking playing systems Czech football team U19 on the elite qualification European championship. Objectives: In this bachelor thesis I will focus on the identification of attack systems in football and the detailed analysis of players' participation in shoot attempts. Method used: Observational analysis with the method of indirect observation. This is a joint research. Results: From indirect observation records I found out that the most used attack is fast attack (77,3%). Continual attack (13,3%) and combined attack (9,63%) was used rarely. The most attacking playing system that was finished was fast attack (23,1%). The most participate players at finished attacks were middle defenders, midfielders and forwards. Keywords: Fast attack, football, combined attack, continual attack
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Role of the mitochondrial pathway in apoptosis induction by taxanes in breast cancer cells
Schmiedlová, Martina ; Kovář, Jan (advisor) ; Anděra, Ladislav (referee)
Apoptosis represents one of the cell death mechanisms which is realized after the application of taxanes in breast cancer cell lines. Apoptosis induction can be principally triggered either by outer or inner pathway. The aim of the diploma thesis is to contribute to the elucidation of role and mechanisms of the inner mitochondrial pathway of apoptosis induction after taxane application (paclitaxel and SB-T-1216) employing a model of breast carcinoma cell lines SK- BR-3 (nonfunctional p53, functional capase-3) and MCF-7 (functional p53, nonfunctional caspase-3). Specifically, we tested the effect of both employed taxanes on mitochondrial membrane potential, ROS level and the expression and localization of proteins regulating inner mitochondrial pathway. Taxane application resulted in mitochondrial membrane dissipation in SK-BR-3 cell line. However, this was not shown in MCF-7 cell line. We found no changes in Bax and Smac/DIABLO expression after taxane application in both tested cell lines. There was a decrease of Bid expression after taxane application in SK-BR-3 line, but not in MCF-7 line. Taxane application did not lead to the translocation of Bax and Bid (tBid) proteins from cytosol to mitochondria in both tested cell lines. Similarly, there was no Smac/DIABLO release from mitochondria to...
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