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The role of cytoskeleton in movement and navigation of neuronal growth cones
Olekšák, Adam ; Libusová, Lenka (advisor) ; Weissová, Romana (referee)
Growth cone is a dynamic structure localized at the tips of growing neurites. It detects guidance cues in the extracellular environment and enables growing neurite to properly respond to them. Cytoskeleton plays a key role in navigation of growing neurite. Microtubules and microfilaments enable the motion of the growth cone by generating force acting on the cytoplasmic membrane as well as on the substrate on which the neuron grows. Microfilaments are located mainly in the periphery of the growth cone. They are more dynamic than microtubules, and their polymerization and depolymerization enable formation of dynamic processes on the growth cone. These are used by neurons to gain information about their surroundings and for formation of adhesions on permissive substrates. Adhesions facilitate the growth of neurites. Direction, timing and speed of formation of the dynamic processes are regulated by a number of actin-associated proteins. These proteins are common targets of signalling pathways that are induced by activation of growth cones' cytoplasmic membrane-bound receptors by guidance cues. Along the microfilament bundles, microtubules enter the periphery of the growth cone aided by crosslinking and motor proteins. Microtubules are necessary for reducing the growth cone dynamics, the first step in...
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Mitochondrial dynamics in myocardium.
Weissová, Romana ; Nováková, Olga (advisor) ; Kalous, Martin (referee)
The heart is an absolutely vital body organ, which requires sufficient amount of active mitochondria for its energy demanding activity. The functionality of a mitochondrial population is maintained through mitochondrial turnover, encompassing mitophagy removing damaged mitochondria and mitochondrial biogenesis responsible for the emergence of new organelles. Dynamic processes of mitochondrial fusion and fission can also contribute to the maintenance of a healthy mitochondrial population. Mitochondrial fusion and fission have not yet been proven in cardiomyocytes, although these cells possess all the proteins required for these events. These processes, however, take on the importance during pathological conditions, when changes in the amount of protein applied in the mitochondrial dynamics occur. The modification in mitochondrial phenotype leads to the cell damage. Understanding the role of mitochondrial dynamics in myocardium may contribute to the development of new heart diseases treatments.
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The role of mitochondria in adaptation to chronic hypoxia in the spontaneously hypertensive and conplastic rats.
Weissová, Romana ; Kalous, Martin (advisor) ; Rauchová, Hana (referee)
Adaptation to chronic hypoxia provides cardioprotective effects. Molecular mechanism of this phenomenon is not yet completely understood, but it is known that cardiac mitochondria play an essential role in induction of protective effects. The purpose of this diploma thesis is to study effects of continuous normobaric hypoxia (CNH; 10 % O2, 21 days) on spontaneously hypertensive rats (SHR) and conplastic strain that is derived from SHR. These animals have nuclear genome of SHR strain and mitochondrial genome of Brown Norway (BN) strain. Cardiac homogenate was used to measure enzymatic activity of malate dehydrogenase (MDH), citrate synthase (CS), NADH-cytochrome c oxidoreductase, succinate-cytochrome c oxidoreductase and cytochrome oxidase (COX). Using Western blot procedure the protein amount of antioxidant enzymes was measured - manganese superoxide dismutase and copper-zinc superoxide dismutase (MnSOD, Cu/ZnSOD), catalase and chosen subunits of oxidative phosphorylation complexes (Ndufa9, Sdha, Uqcrc2, COX-4, MTCO1, Atp5a1). Under normoxic conditions the conplastic strain has lower amount of complex IV subunit MTCO1 in comparison with SHR. This subunit is encoded by mitochondrial DNA and it is one of the seven protein-coding genes in conplastic strain that differ from SHR. Adaptation to hypoxia causes an...
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Cell therapies designed to restore radiation-induced brain injury
Nuriakhmetova, Elina ; Zíková, Martina (advisor) ; Weissová, Romana (referee)
Neural stem cells are undifferentiated cells that are defined by their replication potential and their ability to differentiate into different types of neuronal and glial cells. The adult brain contains two neurogenic zones located in the subventricular zone of the lateral ventricles and in the dentate gyrus of the hippocampus. In both of these zones, neural stem cells produce new neurons. The subject of the bachelor thesis is a summary of current knowledge about neural stem cells and molecular mechanisms underlying changes in neurogenic zones after radiotherapy. At the same time, cell therapies used to minimize damage associated with radiation are discussed.
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Trimeric G protein-regulated signaling in neurodegenerative processes
Daňková, Karolína ; Novotný, Jiří (advisor) ; Weissová, Romana (referee)
Members of the large family of G proteins and their coupled receptors are involved in a variety of transduction processes the cell uses to respond to a received signal. Depending on their specific structure and function, they influence a wide range of effector molecules. A large body of research has shown that many neurodegenerative diseases have a negative impact on the signal pathways controlled by G proteins. Due to ageing population, neurodegenerative diseases are currently imposing a risk for growing numbers of people. The sequelae observed in the pathological development of such diseases include especially changes in membrane receptors representation or receptor uncoupling from G protein, which inhibits G subunits activation. The undesirable inhibition or over-stimulation of G proteins results in the increase or decrease in effector activity, which subsequently impacts the production of second messengers and the activity of subsequent members of the signal cascade. As a result, these alterations lead to an increase in intracellular concentration of Ca2+ ions, which then influence receptors responsible for excitotoxicity, and contribute to apoptosis and necrosis of neuronal population. The thesis summarizes the defects of signalling pathways controlled by trimeric G proteins in association...
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The role of mitochondria in adaptation to chronic hypoxia in the spontaneously hypertensive and conplastic rats.
Weissová, Romana ; Kalous, Martin (advisor) ; Rauchová, Hana (referee)
Adaptation to chronic hypoxia provides cardioprotective effects. Molecular mechanism of this phenomenon is not yet completely understood, but it is known that cardiac mitochondria play an essential role in induction of protective effects. The purpose of this diploma thesis is to study effects of continuous normobaric hypoxia (CNH; 10 % O2, 21 days) on spontaneously hypertensive rats (SHR) and conplastic strain that is derived from SHR. These animals have nuclear genome of SHR strain and mitochondrial genome of Brown Norway (BN) strain. Cardiac homogenate was used to measure enzymatic activity of malate dehydrogenase (MDH), citrate synthase (CS), NADH-cytochrome c oxidoreductase, succinate-cytochrome c oxidoreductase and cytochrome oxidase (COX). Using Western blot procedure the protein amount of antioxidant enzymes was measured - manganese superoxide dismutase and copper-zinc superoxide dismutase (MnSOD, Cu/ZnSOD), catalase and chosen subunits of oxidative phosphorylation complexes (Ndufa9, Sdha, Uqcrc2, COX-4, MTCO1, Atp5a1). Under normoxic conditions the conplastic strain has lower amount of complex IV subunit MTCO1 in comparison with SHR. This subunit is encoded by mitochondrial DNA and it is one of the seven protein-coding genes in conplastic strain that differ from SHR. Adaptation to hypoxia causes an...
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Mitochondrial dynamics in myocardium.
Weissová, Romana ; Nováková, Olga (advisor) ; Kalous, Martin (referee)
The heart is an absolutely vital body organ, which requires sufficient amount of active mitochondria for its energy demanding activity. The functionality of a mitochondrial population is maintained through mitochondrial turnover, encompassing mitophagy removing damaged mitochondria and mitochondrial biogenesis responsible for the emergence of new organelles. Dynamic processes of mitochondrial fusion and fission can also contribute to the maintenance of a healthy mitochondrial population. Mitochondrial fusion and fission have not yet been proven in cardiomyocytes, although these cells possess all the proteins required for these events. These processes, however, take on the importance during pathological conditions, when changes in the amount of protein applied in the mitochondrial dynamics occur. The modification in mitochondrial phenotype leads to the cell damage. Understanding the role of mitochondrial dynamics in myocardium may contribute to the development of new heart diseases treatments.
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