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The role of SGK1 in heart
Havlíková, Nikola ; Horníková, Daniela (advisor) ; Mančíková, Andrea (referee)
Serum and glucocorticoid-regulated kinase 1 (SGK1) is an enzyme which is encoded by the sgk1 gene. This is a dimer. Generally, SGK1 belongs into the protein kinases, but its structure is somehow different from the other protein kinases, especially in the reaction center, which is related to its activity. SGK1 belongs to the subfamily of serine/threonine kinases. This kinase is activated by insulin or growth factors via phosphatidylinositol-3-kinase (PI3K) and mammalian rapamycin mTORC2. SGK1 plays an important role in inflammatory processes, the proliferation and apoptosis. In heart it helps to increase the abundance of proteins, which has affect on the morphology of ion channels and Na+ /K+ -ATPase. The sgk1 gene plays an important role in cellular stress response. This kinase activates potassium, sodium, chloride and calcium channels, which suggests about the involvement in the regulation of processes such as the cell survival, neuronal excitability and renal sodium excretion. Currently, the most discussed roles of SGK1 are in the heart, kidneys, brain, lungs and gastrointestinal tract. In recent years, it was found that SGK1 has different expression and regulation during the developmental stages and pathological conditions such as hypertension, diabetic neuropathy, ischemic trauma and...
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Factors influencing weight gain in pregnncy
Vodrážková, Nicole ; Kaňková, Šárka (advisor) ; Horníková, Daniela (referee)
In this bachelor thesis I described different factors influencing weight gain in each trimester of pregnancy. There are factors influenced by a lifestyle, such as diet, physical activity, smoking, and BMI before pregnancy. There are also factors which are given individual dispositions, changes in metabolism and hormonal status of the organism. On this basis, this thesis deals with the consequences, that has excessive or insufficient weight gain in pregnancy for the mother and her fetus.
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The role of PGC1 in cardioprotective mechanisms
Jeřábková, Adéla ; Horníková, Daniela (advisor) ; Kolář, David (referee)
One of the leading causes of death worldwide is cardiovascular diseases. Researchers are, therefore, dealing with the mechanisms that induce a cardioprotection. Cardioprotection is a general pathophysiological term under which we understand myocytes protection against damage by ischemia and subsequent reperfusion impairment, inflammation, hypertension, and toxic and degenerative changes, including some types of apoptosis. One of the less common ways of cardioprotection is a cold adaptation. Adaptive thermogenesis is an important part of energy homeostasis and protection against obesity, metabolic disorder threatening heart. The PGC family of proteins plays a very important role in adaptive thermogenesis. This thesis summarizes the current state of literature in cold adaptation issues, especially the role of PGC1α and its effects at the cellular and tissue level. mRNA expression of PGC-1α is strongly induced in brown fat and skeletal muscles of mice exposed to cold. PGC-1α also increases the transcriptional activity of PPAR-γ and thyroid hormone receptor protein on UCP-1 (uncoupling protein). UCPs (uncoupling proteins) are small proteins localized to the inner side of the mitochondrial membrane to facilitate the transport of protons, which they release into concentration gradient without ATP...
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Effect of physical exercise on adipose tissue characteristics: influence of obesity and aging
Čížková, Terezie ; Šiklová, Michaela (advisor) ; Horníková, Daniela (referee)
Obesity and ageing are associated with the changes in adipose tissue characteristics, which are con- sidered as one of important contributors to development of complications, such as cardiovascular diseases or type 2 diabetes. Physical exercise is known to be effective in prevention of diseases rela- ted to obesity and ageing. However, the effect of exercise on adipose tissue characteristics is only few elucidated in humans. The goal of this bachelor thesis is to summarize the main effects of exer- cise on adipose tissue characteristics. This thesis subsequently discuss detrimental changes (dysfunction) of the adipose tissue in obesity. Recent findings about the effects of some types of physical training on health of the elderly people are also mentioned. The initial chapter deals with adipose tissue in general, concretely the morphology, metabolism and endocrine function of the adipose tissue are described. Next part is focused on obesity, the concept of a chronic low-grade inflammatory state is introduced. The key section is the fourth chapter, in which the effects of exer- cise on adipose tissue, i.e. effects on metabolism of adipocytes and activation of immune cells, are reviewed. At the end of this thesis, the pathophysiological changes in inflammatory state and adi- pose tissue distribution associated...
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Cellular senescence escape mechanisms - anti-cancer barrier
Davidová, Eliška ; Hodný, Zdeněk (advisor) ; Horníková, Daniela (referee)
Cancer is one of the most dangerous diseases of the modern world. Therefore, many world laboratories engaged in research into the causes leading to the outbreak of this insidious disease. In this context, it has already been found that the normal animal cells do not divide indefinitely, but have a finite replicative life span. After this period, cells undergo either apoptotic processes or enter into so-called senescence, typical for proliferation arrest, but preserved metabolic processes. Further research has revealed that senescence serves as an effective anticancer program and currently is shed light on its significance in relation to various physiological or pathological processes associated with aging. In this work, the focus is on the role of senescence as a barrier for cancer development, and effectiveness. It can be assumed, that if the senescent cycle arrest functioned perfectly, the incidence of cancer among people would be recorded in much lower extent. The aim of this thesis is the current knowledge about the physiological and pathological roles of senescence and possible causes of overcoming this barrier, the result may be the uncontrolled cell division and tumorigenicity.
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Inhibition of 11β-hydroxysteroid dehydrogenase 1 in hippocampus
Kvapilová, Pavlína ; Pácha, Jiří (advisor) ; Horníková, Daniela (referee)
This diploma thesis deals with the inhibition of 11-hydroxysteroid dehydrogenase 1 in the hippocampus. The aim was to determine whether the selected inhibitors with intraperitoneal administration pass through the blood-brain barrier, to determine the time course of inhibition of hippocampal 11-HSD1, to compare the efficacy of different inhibitors and to find out plasma concentrations of the most effective inhibitors and compare them with plasma concentrations of glucocorticoids. Selected inhibitors were emodin, quercetin, glycyrrhetinic acid and substituted adamantyl C544. The most significant effect on the inhibition of 11-HSD1 demonstrated nonselective inhibitor glycyrrhetinic acid and selective inhibitor substituted adamantyl C544. By comparing the plasma levels of these inhibitors, and the plasma levels of glucocorticoids was found that the selective inhibition by the C544 does not affect the overall level of corticosterone, and thus the activity of the HPA axis, which makes it important potent inhibitor of 11-HSD1 suitable for further studies. Key words 11-hydroxysteroiddehydrogenase 1, HPA axis, glucocorticoids, hippocampus, inhibition, emodin, quercetin, glycyrrhetinic acid, substituted adamantyl C544
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Control of creatine kinase activity due to structural changes of the enzyme molecule
Horníková, Daniela
Myofibrillar creatine kinase (CK) has been studied for activity control due to structural changes of its molecule. Data indicating three CK conformations for three substrate ligation states were collected, using fluorescence and absorption spectroscopy. As the radius of CK molecule under ligation states: CK free, CK-ATP+creatine and CK-ATP complexes decreases, in the same block sequence decrease: fluorescence lifetimes 2.72, 2.42, 2.38 ns of intrinsic tryptophans emission, anisotropy decays, rotation correlation times 35, 29, 27 ns and acrylamide quenching. Data were confirmed by anisotropy experiments with CK-(FITC labelled), providing the correlation times 34, 30, 27 ns. Results indicate that besides the "energy minimizing" conformational effects of substrates, other essential components of physiological control at the subcellular level should be involved in the transition of the CK- ATP+creatine complex from the intermediary (nonreactive) to the closed (reactive) conformation of the molecule. Keywords: creatine kinase, conformational effect of substrates, enzyme activity control.
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