National Repository of Grey Literature 36 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Mitochondrial bioamarkers in Huntington's disease
Vizelka, Vera ; Hansíková, Hana (advisor) ; Dračínská, Helena (referee)
Huntington' s disease (HD) is a severe hereditary neurodegenerative disorder. The cause of this disease is a mutation of the gene that codes the protein huntingtin (htt). The mutation manifests itself as an abnormal extension of CAG triplets. In this way, a polyglutamine chain is formed in the htt molecule, which causes its fragmentation and aggregation. The result is a misfolded protein and this results in damage of neurons, especially in the area of striatum. The biochemical basis of neuronal death has not yet been clarified. Today, there is no effective treatment for HD. Htt participates in many different cellular processes, for example it participates in the regulation of transport events in the cell, participates in the transcription of some genes and also controls apoptosis. Mutated htt can be the cause of mitochondrial dysfunction. The consequence of the action of mutated htt is the occurrence of oxidative stress and subsequently the onset of the neurodegeneration process, but the exact state of mitochondria during the development of the HD has not yet been carefully investigated. Previous studies have studied mitochondrial disorders not only in the brain, but also in other extraneuronal tissues. The aim of the bachelor's thesis was to optimize the preparation of a sample from buccal smear...
Congenital disorders of glycosylation and their impact on cellular and energetic metabolism
Rychtárová, Lucie ; Hansíková, Hana (advisor) ; Hodek, Petr (referee) ; Pecinová, Alena (referee)
Inherited disorders of glycosylation (CDG) are a large group of more than 160 types of metabolic disorders caused by genetic defects that lead to impaired glycan biosynthesis and modification. The lipid dolichol plays an essential role in glycan biosynthesis. Glycans play a key role in the function and structure of proteins and lipids and their deficiency leads to severe clinical symptoms. CDG usually manifests in childhood as a multisystem disorder. Families thus face a serious health problem due to the progressive and highly variable nature of the disease, the unfavorable prognosis and, with few exceptions, the unavailability of treatment. Currently, we still do not have a sufficient range of methods to recognize rare types of CDG and our knowledge of the pathophysiology of CDG is still limited. The first aim of this work was to optimize the method of determination of dolichol isoforms and to study them in physiology and pathology. The second aim of the work was to investigate the bioenergetic status and overall metabolism in the most common type of CDG - deficiency of phosphomannomutase 2 (PMM2-CDG), and in CDG caused by a defect in dolichol biosynthesis. The distribution of urinary dolichol isoforms in the population was characterized using an optimized method. The dolichol isoforms profile...
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...
The study of energetic metabolism in patients with mitochondrial translation defects
Hýbl, Martin ; Hansíková, Hana (advisor) ; Čermáková, Michaela (referee)
Mitochondria are semi-autonomous organelles that contain their own DNA. Human mitochondrial DNA (mtDNA) encodes a total of 37 genes: 13 subunits of oxidative phosphorylation complexes (OXPHOS), 22 transfer RNA (tRNA) molecules and 2 ribosomal RNA (rRNA) molecules. Pathogenic mutations in genes associated with mitochondrial translation are a common cause of mitochondrial disease. These mutations can be found in mtDNA or in nuclear genes encoding ribosomal proteins, initiation, elongation and termination factors, mitochondrial tRNA-modifying enzymes and aminoacyl-tRNA synthetases. Mitochondrial aminoacyl-tRNA synthetases (mt-aaRS) are enzymes that catalyse the addition of single amino acids to specific tRNAs. The aim of the bachelor thesis was an introduction to the work in the tissue culture laboratory. To prepare samples for the following experiments, skin fibroblasts from five patients with mt-aaRS disorders (AARS2, DARS2, NARS2, SARS2) and control lines were cultured in glucose and galactose media. Subsequently, the procedure for determining the equilibrium amount of selected subunits of the OXPHOS complexes was optimized and applied to the analysis of fibroblasts from five patients with mt-aaRS disorder. When the cells were cultured in glucose medium, decreased levels of some subunits of complex...
Modulation of Mitophagy in Huntington Disease
Šonský, Ivan ; Hansíková, Hana (advisor) ; Kalous, Martin (referee)
Huntington diseases (HD) is a hereditary neurodegenerative disorder characterized by the presence of the aggregation prone mutated version of protein huntingtin (HTT). Mutation in huntingtin (mHTT) results in an aberrant expansion of the polyglutamine tract, thereby gaining toxic properties, which causes progressive loss of striatal medium spiny neurons. Neurons heavily rely on a healthy mitochondrial pool. Thereby, it is crucial to preserve biological mechanisms maintaining its turnover and quality control, such as mitophagy. However, mHTT impairs mitophagy, therefore preventing autophagosomes from engulfing mitochondria and resulting in an accumulation of dysfunctional mitochondria. Our recent results showed that mHTT-caused mitochondrial impairments can be observed in more easily accessible extraneuronal cells such as skin fibroblasts. While mitophagy is considered a fundamental cellular process, there is a lack of compounds selectively modulating mitophagy. Thereby, the aim of this diploma thesis was to introduce a small-molecule compound, MIND4-17, which showed neuroprotective effects in HD, and to study its selective effect on mitophagy in cultivated fibroblasts from HD patients and controls. Here we report that MIND4-17 increased the expression of specific autophagy markers in fibroblasts...
Complex I of mitochondrial respiratory chain a its disorders.
Rodinová, Marie ; Hansíková, Hana (advisor) ; Kalous, Martin (referee)
NADH: ubiquinone oxidoreductase (Complex I) is a multisubunit protein complex of inner mitochondrial membrane. Complex I is the biggest and most complicated part of oxidative phosphorylation system, which is responsible for the cell ATP production. It consists of 45 subunits. 7 subunits are mitochondrial encoded, remainder 38 are nuclear encoded. NADH: ubiquinone oxidoreductase has L-shaped structure, which is built of two arms: membrane arm and matrix located peripheral arm. Complex I oxidize the NADH molecule. The electron transport is coupled with proton pumping across the inner mitochondrial membrane to intermembrane space, where proton gradient developed and which is used by ATP synthase to ATP synthesis. Deficiencies of NADH: ubiquinone oxidoreductase represent extensive, clinically and genetic heterogeneous group of mitochondrial diseases. Decrease of activity and amount of complex I, decrease of ATP production, changes of membrane potential, mitochondrial morphology and mitochondrial network and increasing of production of reactive oxygen species are found in cells with defects of NADH: ubiquinone oxidoreductase. Combination of this features lead to serious illnesses, which are almost fatal and we still haven't any useful therapy. Aim of this study is to summarize present knowledge about...
Fumarate hydratase as tumor suppressor
Kedrová, Kateřina ; Hansíková, Hana (advisor) ; Befekadu, Asfaw (referee)
1 Abstract Fumarate hydratase (fumarase, EC catalyzes the reverse hydration of fumarate to S malate. In mammalian cells, it changes fumarate in the mitochondrial matrix as a part of the citric acid cycle and in the cytosol, where functions to metabolize fumarate the product of the degradation of some amino acids, of ammonia transformation to urea acid or of the purine nucleotide synthesis. . In human cells, fumarase is encoded by FH gene localized on chromosome 1 (1q42.1). The FH gene consists of 10 exons and encodes for a 510 amino acids-long protein including the N-terminal mitochondrial signal sequence. Germline heterozygous FH mutations were found in two autosomal dominant syndromes. These are multiple cutaneous and uterine leiomyomatosis (MCUL1 or MCL) and hereditary leiomyomatosis and renal cell cancer (HLRCC). In the most of tumors from these patients, loss of FH gene heterozygosity was also found. It has been suggested that fumarase acts as a tumor suppressor according to Knudson's two-hit hypothesis. The aim of the bachelor thesis was to study the activity and amounts of fumarase in a series of 22 samples of uterine leiomyomas from 22 young women patients (21-31 years) with sporadic uterine leiomyomas. As a control sample, uterine leiomyoma from a 38-year-old patient was used. Activity of...
Study of mitochondrial ultrastructure and functions in selected mitochondrial and lysosomal storage disorders
Kostková, Olga ; Hansíková, Hana (advisor) ; Šmíd, František (referee) ; Hyánek, Josef (referee)
This thesis has been worked out in The laboratory for study of mitochondrial disorders (Departement of Pediatrics, 1st Faculty of Medcine, Chales university in Prague) and in cooperation with The Institute of Inherited Metabolic Disorders. Mitochondrial disorders represent a heterogeneous group of diseases with the onset at any age from neonatal period till adulthood, mostly presented with very severe clinical courses of disease. The mammalian organism is fully dependent on mitochondrial oxidative phosphorylation system as on the major energy producer of the cell. Therefore the mitochondrial disorders affect mainly high energy demanded tissues such as brain, heart or muscle. Simillar phenotype is observed in many lysosomal storage disorders. Despite of expanding knowledge of molecular basis of mitochondrial and lysosomal disorders, it may be still difficult to explain the exact pathogenesis of disease as well as the prognosis for patients and their families. Mitochondrial functions affect more than just energy production; they contribute in initiation of apoptosis, in cellular calcium homeostasis, and in production of reactive oxygene species. Disturbed mitochondria become a goal of autophagy mediated by the lysosomal compartement. The results of our study enable: 1. better understanding of the tissue...

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1 Hansíková, H.
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