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Characterization of Cbf11 and Mga2 interactions in the fission yeast
Grulyová, Michaela ; Převorovský, Martin (advisor) ; Čáp, Michal (referee)
Transcription factor Cbf11 belongs to the CSL protein family. The CSL protein family is well known for its function in Notch signalling pathway, however representatives in Notch- less fission yeast were discovered. Mga2 protein is a transcription regulator of triacylglycerol and glycerophospholipid metabolism. A crosstalk between Cbf11 and Mga2 was found. Cbf11 and Mga2 share target genes, and both are required for mitotic fidelity. This thesis aims to validate and characterize relationship between these transcription regulators. We show here that protein levels of Cbf11 and Mga2 change in response to presence of the other protein, as well as in response of nitrogen source. We also determine phylogenetic distribution of Cbf11 and Mga2 among Fungi, pointing to its connection. Using proteomic analysis of mga2 and cbf11 deletion strains we found that there is an overlap between proteins up/downregulated in these strains. Together, these results acknowledge crosstalk between Cbf11 and Mga2 proteins, bringing a novel connection between CSL protein family member and a functional analogue of mammalian SREBP-1 protein Mga2.
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Charakteristika přeměny larvální tukové tkáně v průběhu metamorfózy u \kur{Drosophila melanogaster}
DANIELOVÁ, Adéla
The main aim of this master thesis is a characterization of morphological and physiological changes of larval adipose tissue in Drosophila melanogaster by using histological technics. Moreover, the expression of genes involved in lipolysis, mobilization of lipids, and ceramides metabolism were analyzed. The theoretical part of this thesis provides the current knowledge about the function of the larval fat body, the formation of lipofuscin, and the role of genes involved in lipid and ceramide metabolism. In the practical part, the results of characterization of adipocytes size changes and changes of size and quantity of lipofuscin granules and lipid droplets during the metamorphosis and post-metamorphosis, are introduced. Furthermore, it involves the analysis of genes expression being essential for lipid metabolism and mobilization of lipid storage.
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Characterization of closed mitosis in the fission yeast Schizosaccharomyces pombe with perturbed lipid metabolism
Hohoš, Patrik ; Převorovský, Martin (advisor) ; Cebecauer, Marek (referee)
[EN] The division of an eukaryotic cell is mediated by the process of mitosis. It is a complex cellular process which needs to be highly regulated. In contrast to the mammalian open type of mitosis when nuclear envelope is disassembled, fission yeast Schizosaccharomyces pombe undergoes closed mitosis inside the intact nuclear compartment. Cell nucleus undergoes morphological changes as a common sphere-shaped nucleus stretches upon mitotic spindle activity forming typical dumbbell structure. Further tension results in the separation of two daughter nuclei. Such extensive changes in the nuclear envelope surface demand a sufficient supply of membrane phospholipids. Cells with perturbed lipid metabolism are unable to meet such a demand and the mitotic division in these cells usually results as a catastrophic mitotic event or CUT (Cell Untimely Torn) phenotype. Moreover, recent studies show genetic interactions between the deletions of the lipid gene regulator cbf11 and factors maintaining the centromere chromatin structure. Surprisingly, rescue of CUT phenotype has been recently reported after the deletion of several factors contributing to the centromeric H3K9 epigenetic modifications in the cells lacking the transcription factor Cbf11. Here we show no rescue of CUT phenotype after the deletion of...
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The possibilities of physical exercise in relation to the metabolism after spinal cord injury
Olišarová, Eva ; Hlinková, Zuzana (advisor) ; Kříž, Jiří (referee)
The goal of this bachelor thesis is to summarize the information about the possibilities of the physical exercise in individuals with the spinal cord injury. The work presents various types of the physical activity and describes their effect on metabolism and body composition. It also includes the information about the frequency, the duration and the intensity of exercise. The interruption of the somatomotor and somatosensory pathways in patients with spinal cord injury leads to the reduction of their physical activity. As a consequence of that, their metabolic profile and body composition get worse. Early after the injury, the patients suffer from the massive muscle atrophy and the rise of the amount of adipose tissue. These changes have a negative effect on metabolism of lipids and carbohydrates. It results in the development of dyslipidaemia and insulin resistance, sometimes even in type 2 diabetes mellitus. These secondary complications worsen the quality and the length of life of the patients with the spinal cord injury. Better understanding of these issues is necessary to improve the quality of health care for these people. The work includes a short questionnaire. Its goal is to describe the current situation of patients with the spinal cord injury in the Czech Republic. The questionnaire was...
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Crosstalks between nitrogen metabolism, the TOR pathway and the metabolism of lipids
Grulyová, Michaela ; Převorovský, Martin (advisor) ; Maršíková, Jana (referee)
Cells coordinate their metabolism based on various factors, for example nitrogen availability. The TOR pathway is an important regulator of nitrogen metabolism, it has a role in sensing intracellular amino acids status, and it controls especially cell growth, protein synthesis, proliferation and cell survival. However, it has been shown that the TOR pathway also controls lipid biosynthesis and lipid accumulation through various mechanisms in response to nitrogen availability. Although the TOR pathway is well conserved among the eukaryotic organisms, its outcomes differ diametrically when it comes to the lipid accumulation. This essay provides some insides into the mechanisms of regulation of the lipid metabolism by the TOR pathway.
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Evolutionarily conserved mechanisms of gene expression regulation by nuclear receptors.
Chughtai, Ahmed Ali ; Kostrouch, Zdeněk (advisor) ; Malínský, Jan (referee) ; Brábek, Jan (referee)
Transcriptional regulation of gene expression in eukaryotes has evolved over millions of years. The regulatory pathways of nuclear receptors represent an evolutionarily ancient, but conserved mechanism with associated accessory proteins, many of them forming a functional nexus known as the Mediator complex involved in transcription. Despite the versatility of the pathway, e.g. through the adoption of new regulatory functions in phylogenetically more recent Metazoa, we hypothesise that the intrinsic potential of the NR-Mediator axis to directly translate a stimulus to a biological response is conserved across species, and additional regulation could also be achieved through secondary functions of its essential members. To support the hypothesis, we assessed the ligand-binding capability of retinoic X receptor in Trichoplax adhaerens and provided evidence to support the concept that this capability was already present at the base of metazoan evolution. With regards to the potential secondary functions, we took inspiration from previous research and identified the Mediator subunit 28 (MED28) as the only known member having documented nuclear and cytoplasmic dual roles, and thus possessing the potential to transmit signals from the cellular structural states to the nucleus. Due to the lack of...
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Comparison of eating habits of patients with familial hypercholesterolemia and mixed dyslipidemia
Holubová, Šárka ; Šnejdrlová, Michaela (advisor) ; Altschmiedová, Tereza (referee)
This bachelor thesis deals with eating habits of patients with two metabolic diseases, familial hypercholesterolemia and mixed dyslipidemia. The thesis is divided into two parts. The first theoretical part summarizes information on metabolic disease, types of treatment and dietary measures. The second, practical part is also divided into two parts. In the retrospective part, the entry and exit values of lipidograms of 21 patients with familial hypercholesterolemia and 14 patients with mixed dyslipidemia are compared. The pacients have been treated in the Center of Preventive Cardiology. The results show that total cholesterol, LDL-cholesterol and triglyceride levels are reduced after the pharmacological treatment in both groups. HDL- cholesterol remains unchanged. There are no changes in the lipidograms by patients who do not have pharmacological treatment. In the second part, the dietary habits of 8 patients, 4 with the familiarity of hypercholesterolemia and 4 with mixed dyslipidemia, are discussed qualitatively, where it is evident that nutritional education is insufficient because only two patients have visited a nutritional therapist at least once. keywords: familial hypercholesterolemia, mixed dyslipidemia, lipid metabolism, nutrition
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Intramembrane proteases and their medical significance
Deylová, Anna ; Stříšovský, Kvido (advisor) ; Macůrková, Marie (referee)
Intramembrane proteases are membrane enzymes whose active site is buried below the surface of the biological lipid membrane, and which cleave other membrane proteins within their transmembrane domains. They are divided into four families according to their catalytic residues - aspartate, serine (often called rhomboids), metalloproteases and the recently described glutamate proteases. By proteolytic cleavage inside lipid bilayer they affect many significant biological processes such as metabolism of lipids, cell proliferation and adhesion, regulation of developmental signaling, degradation of signal peptides, and membrane protein quality control. This work focusses on the role of intramembrane proteases in various diseases and biological mechanisms associated with pathological processes. These are specifically Alzheimer's disease, infection by unicellular parasites (Mycobacterium tuberculosis, Entamoeba histolytica and Plasmodium falciparum), maturation of hepatitis C virus, Bunyamwera virus and swine influenza virus, and mitochondrial dysfunction.
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Synthesis of ligands for farnesoid X receptor
Kašpar, Miroslav ; Chodounská, Hana (advisor) ; Kasal, Alexander (referee)
Farnesoid X receptor is mostly expressed in liver cells and its activation may be used for the treatment of cirrhosis causing diseases, especially biliary cirrhosis and nonalcoholic steatosis. These two latter diseases are most common in developed countries and, as of date, no effective treatments are available. Therefore, the aim of this project is the design and synthesis of novel bile acid analogues with subsequent biological evaluation towards farnesoid X receptor. Thus, a series of new compounds were designed using computational modeling studies and chemical synthesis was done to develop structure-activity relationships. Chemical structure analysis and purity was confirmed by conventional analytical methods. Finally, synthetic compounds were profiled against farnesoid X receptor in collaboration with the Pharmaceutical faculty of Charles University in Hradec Králové. Keywords: farnesoid X receptor, FXR, bile acids
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The role of the gastrointestinal hormones in the control of energy homeostasis
Myšáková, Michaela ; Horáková, Olga (advisor) ; Ergang, Peter (referee)
Zachování tělesné homeostázy vyžaduje precizní komunikaci mezi všemi buňkami organismu. Velkou měrou k tomu přispívají gastrointestinální hormony, které jsou významnými signálními molekulami a podílejí se na distribuci i zpracování přijatých živin. Každý h typem buněk a jeho sekrece je regulována v závislosti na přítomnosti konkrétních nutrientů. Vzhledem rozdílné anatomii jednotlivých částí gastrointestinálního traktu, je lokalizace buněk produkujících šná. Účinky gastrointestinálních hormonů jsou rozmanité a hrají důležitou roli energetické kontrole organismu. Některé hormony (gastrin) působí jen lokálně, naproti tomu jiné (inkretiny, ghrelin) jsou zapojeny do signalizace přes centrální i periferní ne do signalizace nervové soustavy umožňuje těmto hormonům podílet se na regulaci pocitu hladu a mnoha onemocněními. V důsledku nevyváženého příjmu živin (například při nadměrném příjmu lipidů nebo sacharidů) dochází narušení některé ze složek hormonálního regulačního systému a následně vzniku onemocnění. Nejznámějšími onemocněními, vzniklými v důsledku nutriční a následně hormonální dysbalance, jsou například inzulínová rezi hormony je naprosto klíčová pro zachování lipidového metabolismu i glukózové homeostázy. Klíčová slova:
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