National Repository of Grey Literature 206 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
The role of mitochondrial DNA in reproduction
Svobodová, Mariana ; Daňková, Pavlína (advisor) ; Jelínková, Ladislava (referee)
The bachelor's thesis focuses on the role of mitochondrial DNA (mtDNA) in human reproduction, especially describing the differences in mtDNA dynamics in oogenesis, spermatogenesis and early embryo development. The physiological function of mtDNA is complemented by its pathologies and their effect on fertility and the ability of the embryo to implant successfully. Furthermore, mtDNA is discussed as a possible diagnostic marker in the evaluation of the quality of sperm, eggs and embryos. These findings of these studies are especially significant for assisted reproduction, where the goal is to select the highest quality embryo with the greatest implantation potential. The work also briefly mentions the presence of cell free mtDNA in the mother's blood and its connection with the development of preeclampsia. Key words: mtDNA, mitochondria, reproduction, (in)fertility
Developmental, pathobiochemical and molecular aspects of selected inborn errors of metabolism
Kolářová, Hana ; Honzík, Tomáš (advisor) ; Drahota, Zdeněk (referee) ; Morava Kozicz, Eva (referee)
Inborn errors of metabolism represent a heterogenous group of rare conditions, most having an incidence of less than 1 in 100,000 births. Because of their low prevalence, they are on the margin of attention of general research and even more so of large pharmaceutical companies. Study of rare diseases is the only way to design therapeutic options in order to improve quality of life of affected patients. Present Thesis particularly focuses on disturbances in mitochondrial energy metabolism. The main goals were the characterization of mitochondrial biogenesis within foetal development, as well as in childhood and adulthood. Another aim was to define clinical, biochemical and molecular aspects of mitochondrial optic neuropathies in childhood and adulthood. This work supported the earlier observations that gestational week 22 is the edge of viability, which has to be taken into account in upcoming discussions about guidelines on resuscitation of preterm neonates. Secondly, over last four years, we managed to examine and describe large cohort of patients with optic neuropathies based on a mitochondrial dysfunction. We have managed to characterize the biochemical and molecular-genetic background in more than 200 patients, and both selected cases (LHON/MELAS overlap syndrome) and cohort studies (MELAS,...
The study of mitochondrial energy-metabolism maturation
Křížová, Jana ; Hansíková, Hana (advisor) ; Pecina, Petr (referee) ; Rauchová, Hana (referee)
During intrauterine development in mammals, the fetus is exposed to a hypoxic environment. To allow proper postnatal adaptation to external conditions, a rapid transition from glycolytic to oxidative metabolism by mitochondria is required in fetal tissues after birth. Mitochondrial maturation is a complex process that is not only transcriptionally regulated. Using techniques such as microarray analysis, quantitative PCR, measurement of enzyme activities or coenzyme Q (CoQ) levels, we have described the acceleration of mitochondrial metabolism in rat liver tissue and skeletal muscle during the perinatal period and correlated the results with those in humans. Of the 1546 rat mitochondrial genes tested, we found statistically significant differences in the expression of 1119 in liver and 827 in muscle. The most significant shift in expression occurred in the rat liver between 20th and 22nd day of gestation, suggesting that the rat fetus is ready for the transition to external conditions at least 2 days before birth. Changes in CoQ levels in both rats and humans show that the amount of CoQ is low inthe prenatal period and increases after birth in both tissues. We have described the atypical kinase Coq8ap as an enzyme whose expression increases significantly after birth. It was previously predicted to...
Mitochondrial structure and energetic metabolism changes in patients with Huntington's disease and in transgenic minipig model
Vanišová, Marie ; Hansíková, Hana (advisor) ; Kalous, Martin (referee) ; Mühlbäck, Alžbeta (referee)
Huntington's disease (HD) is a severe neurodegenerative disease with autosomal dominant inheritance. HD is caused by the expansion of the CAG triplet in the gene for the huntingtin protein (Htt), which leads to damage and loss of its functions. Htt is essential in the development of the nervous system, it is involved in axonal transport, regulation of mitochondrial metabolism gene expression or spermiogenesis. In HD, the nerve tissue is most significantly damaged, but pathological changes associated with the disease are detected throughout the organism. There is currently no satisfactory treatment. Mitochondrial damage has been shown to significantly affect the progression of HD in patients with HD, but the mechanisms of mitopathy and its development with all the effects on tissue physiology in HD are still not fully understood. The aim of the dissertation theses was to study mitochondrial energy metabolism impairment, mitochondrial network organization and mitochondrial ultrastructure in HD in selected tissues of patients with HD and in a minipig model transgenic for HD (TgHD). Furthermore, the effort was to find and characterize a mitochondrial biomarker of HD, which would well reflect the patient's current clinical phenotype state and it would be possible to monitor changes in its parameters...
Effect of lipophilic cation on the toxicity of phosphonium salts in parasitic protists
Čadková, Aneta ; Mach, Jan (advisor) ; Trnka, Jan (referee)
The mitochondrion is an essential organelle responsible for energy metabolism and maintaining cellular homeostasis. Disruption of their function can have serious consequences for the entire cell and organism. Given their key role in the organism, they become an attractive target for drugs. In this thesis, we examine the impact and significance of phosphonium salts as potential mitochondrial-targeted therapeutics. The investigated compounds have modified anchors based on the commonly used triphenylphosphonium cation (TPP+ ). These substances have the ability to permeate the phospholipid bilayer and accumulate on the inner mitochondrial membrane. Our research focuses on selected model organisms of the class Kinetoplastida and opportunistic pathogenic fungi. These pathogenic organisms are responsible for severe infectious diseases in humans. Our aim is to compare the effectiveness of phosphonium salts with different anchor modifications against these organisms and attempt to elucidate their mechanism of action. We have found that the modified salts are capable of inhibiting the growth of parasitic protists at nM concentrations, affecting mitochondrial respiration, membrane potential, and mitochondrial integrity. However, there is no increase in the level of oxygen radicals. We are assuming that the...
Study of mitochondrial morphology in pancreatic β-cells depending on the presence of different types of secretagogues
Lorenc, David ; Dlasková, Andrea (advisor) ; Mráček, Tomáš (referee)
Glucose homeostasis is crucial for the proper functioning of the organism. The pancreatic β-cells, which serve as a sensor of changes in blood glucose concentration and are responsible for the adequate release of the hormone insulin, play a crucial role in its maintenance. Increased glucose concentration activates oxidative phosphorylation and subsequently increases the concentration of cellular ATP, which then indirectly stimulates insulin secretion. The process of oxidative phosphorylation is localized in the inner mitochondrial membrane, where the final stage of processing of substrate energy into ATP occurs. To make the oxidative phosphorylation process as efficient as possible, the mitochondrial network undergoes a series of morphological changes. In this work, we aimed to elucidate the effect of changes in nutrient concentration on mitochondrial morphology in a pancreatic β-cell model, the INS1E tissue line. We used as experimental conditions: 1) a high glucose concentration at which insulin secretion is maximal, 2) a low glucose concentration at which insulin secretion does not occur, and 3) the addition of α-ketoisocaproate, a leucine metabolite that amplifies insulin secretion. We first characterized the bioenergetic parameters that influence mitochondrial morphology. A decrease in glucose...
Mitochondrial transfer and its role in regenerative properties of mesenchymal stem cells
Jaborová, Natálie ; Krulová, Magdaléna (advisor) ; Nahácka, Zuzana (referee)
Mitochondrial transfer represents a form of intercellular communication. In this process, mitochondria are delivered from the donor cell to the recipient cell through several structures. The transfer of mitochondria is observed under pathological and physiological conditions and is accompanied by specific signaling. Mitochondria uptake by injured cells promotes tissue regeneration. This bachelor thesis discusses general knowledge of mitochondrial transfer focusing on mesenchymal stem cells (MSCs) as a donor cell type. Furthermore, the regenerative effect of MSC-derived mitochondria transfer to cells damaged by various pathologies is summarized. In this regard, MSCs have significant therapeutic potential that could be used in future clinical strategies for a number of diseases. Keywords: mitochondria, transfer, mesenchymal stem cells, regeneration
Mechanisms of iron-sulfur cluster biogenesis in eukaryotes
Temešinko, Tomáš ; Doležal, Pavel (advisor) ; Malych, Ronald (referee)
Many essential cellular proteins use iron-sulfur (Fe-S) clusters as cofactors. These proteins often serve as enzymes, components of the electron-transport chain or as intracellular sensors. Prior to the use of the cluster in a protein, it needs to be formed or created de novo. In total, four different mechanisms of Fe-S cluster biogenesis can be used by the eukaryotic cell - ISC, CIA, SUF and NIF. All of these pathways include a specific targeting system for delivering the cluster to its acceptor protein. Errors in biosynthesis ofFe-Sclustersaremostlylethalandcanleadtofailureindevelopmentofmulticellularorganisms.Despite this a better characterization of these mechanisms is needed as research is currently still in progress. This bachelor's thesis provides current information regarding the mechanisms of Fe-S clusters biogenesis in eukaryotes acquired mostly from mammalian cells, including humans, and from well-known model organisms such as Saccharomyces cerevisiae, Arabidopsis thaliana, and parasitic protist Giardia intestinalis.
Selective screening of antiparasitic substances
Wernerová, Klára ; Mach, Jan (advisor) ; Kovářová, Julie (referee)
The mitochondrion is the key organelle of the cell. It is involved in energy metabolism, the Krebs cycle, the respiratory chain, and the formation of Fe-S clusters, which form the structure of many proteins. Therefore, disruption of the mitochondria is usually fatal to the cell, especially if it contains only one mitochondrion, as is the case in Trypanosoma brucei brucei. The T. b. brucei parasite has become the primary model organism for our study because its basic biochemical processes are already well described, including mitochondrial metabolism, and it is also easy to cultivate in the laboratory. Other model organisms we used in this study were Leishmania mexicana, Cryptococcus neoformans and Candida albicans. All these organisms are causative agents of serious diseases, and although there are drugs against them, new drugs need to be developed due to the frequent emergence of resistances. Mitochondria-targeting drugs are promising for the pharmaceutical industry. In this work, we investigate the efficacy of compounds whose structure is composed of a mitochondrial phosphonium anchor linked to a carbon chain. These substances are capable of incorporation into the mitochondrial membranes. The work not only focuses on comparing the potency of the tested substances in selected model organisms, but...
Mitochondrial dysfunction in brain tumors
Rollerová, Kateřina ; Vaňátko, Ondřej (advisor) ; Zobalová, Renata (referee)
Brain tumors are one of the most serious pathologies of the central nervous system. Brain tumors are aggressive and very hard to treat due to the fragile nature of the nervous system, presence of blood-brain barrier and high recurrence rate. One of the hallmarks of brain tumors is mitochondrial dysfunction. Mitochondria are organelles involved in essential cellular processes, such as energy production, redox and calcium signaling, or the regulation of cell death. Structural and functional abnormalities, mutations in the mitochondrial genome and other mitochondrial dysregulations may cause disruptions in various cellular processes, such as production of reactive oxygen species, migration, proliferation, or regulation of cell death, promoting the development and/or maintenance of brain tumors. The goal of this thesis is to summarize current knowledge about mitochondrial dysfunction in brain tumors. Key words: brain tumors; mitochondria; mitochondrial dysfunction; Warburg effect; apoptosis; reactive oxygen species; isocitrate dehydrogenase

National Repository of Grey Literature : 206 records found   1 - 10nextend  jump to record:
Interested in being notified about new results for this query?
Subscribe to the RSS feed.