National Repository of Grey Literature 38 records found  beginprevious24 - 33next  jump to record: Search took 0.00 seconds. 
Biochemical and molecular studies of the congenital disorders of glycosylation
Ondrušková, Nina ; Hansíková, Hana (advisor) ; Stiborová, Marie (referee) ; Hřebíček, Martin (referee)
Congenital disorders of glycosylation (CDG) represent a rapidly growing group of rare inherited metabolic diseases with estimated prevalence as high as 1:20 000, which are caused by genetic defects that impair the process of glycosylation, i.e. the enzymatic addition of a specific saccharide structure onto a protein or lipid backbone. Due to non-specificity and variability of clinical symptoms in the patients, the medical diagnosis of CDG remains extremely challenging and significantly relies on accurate biochemical and genetic analyses. The overall goal of the present dissertation thesis was to study CDG at the biochemical and molecular genetic level in the context of the Czech and Slovak Republic, which involved three specific aims: A.) to introduce and optimize laboratory screening methods for CDG detection in a group of clinically suspected patients, B.) to determine the corresponding genetic defect in the positive patients selected via CDG screening and to study the pathobiochemical aspects of specific CDG types at the cellular level, and C.) to analyze glycosylation disturbances of non- CDG etiology. Contributions of this work include optimization of isoelectric focusing of apolipoprotein C-III (ApoC-III) as a screening method for O-glycosylation abnormalities, as well as the description of...
Effect of biguanides on liver cells metabolism
Švecová, Eliška ; Kalous, Martin (advisor) ; Flachs, Pavel (referee) ; Hansíková, Hana (referee)
The extract from the plant Galega officinalis containing the guanidine derivative galegin has been used in the treatment of diabetes-associated complications since middle ages. Nevertheless, the positive effects of the treatment were often overweight by the adverse side effects. Some sixty years ago guanidin was replaced by the less toxic synthetic biguanide derivatives - metformin, phenphormin and buformin, the latter two being withdrawn due to the unacceptable risk of fatal lactate acidosis. Metformin is still widely used antidiabetics and belongs to the first choice drugs in the treatment of type 2 diabetes. Phenphormin is now gaining renewed attention with regard to its antineoplastic properties. Despite its long-term clinical use the mechanism of biguanides action is not fully understood yet. At present it is generally accepted that the core of its antihyperglycemic effect lays in the inhibition of hepatic gluconeogenesis. In contrast, there is less consensus regarding the particular metabolic pathway or target that are responsible for the metformin-induced attenuation of gluconeogenesis. For a long time, a hot candidate for metformin target in the cell was AMP-activated kinase (AMPK) but the metformin effect was proved also in mice carrying the dominant negative mutation of AMPK α subunit. Quite...
Congenital disorders of glycosylation: alpha -dystroglycanopathies
Zdražilová, Lucie ; Hansíková, Hana (advisor) ; Kubíčková, Božena (referee)
Alpha-dystroglycanopathies are inherited autosomal recessive diseases belonging both to the group of hereditary muscular dystrophies and the congenital disorders of glycosylation. Currently there are 20 genes of which are known to lead to this disease. Alpha-dystroglycan is a membrane protein which is at its mucin domain posttranslationally modified with oligosaccharide chains O-glycosidically bound via mannose. Defective biosynthesis of oligosaccharide chains leads to hypoglycosylation of alpha-dystroglycan, which loses its ability to bind to the laminin G-domain of ligands in extracellular matrix. This hypoglycosylation leads to the group of diseases called alpha-dystroglycanopathies. The most severe forms of alpha-dystroglycanopathies manifest with muscular dystrophy, ocular malformations and defects of central nervous system. Milder forms of this disorder may manifest only with muscular dystrophy without other clinical symptoms. Diagnosis of alpha-dystroglycanopathy is difficult due to the lack of standardly available biochemical methods, which would facilitate the targeting of the investigation process before molecular genetic analysis. The aim of the present study was to provide an overview of alpha-dystroglycanopathies focusing on the structure, alteration and pathology of...
Studium interakcí doplňků stravy s enzymy biotransformace xenobiotik
Bebová, Michaela ; Hodek, Petr (advisor) ; Hansíková, Hana (referee)
Currently, an increasing attention is being paid to phytochemicals as one of the most widely used chemopreventive compounds, generally considered as health-promoting and safe. Flavonoids representing a large group of phytochemicals are present in many dietary supplements formulated from natural sources. The consumption of these concentrated phytochemicals has dramatically increased in the recent decade. It appears, however, that the ingestion of flavonoids might be associated with some adverse effects. Some flavonoids are known modulators of enzymes involved in phase I and phase II metabolism of xenobiotics biotransformation, thus their induction may result in an increase of carcinogen activation. In this study, the effects of selected flavonoid compounds -naphthoflavone, - naphthoflavone, myricetin, and dihydromyricetin, and carcinogens (BaP, PhIP) on phase II metabolism enzymes, sulfotransferases (SULT), have been investigated. To determine the induction of SULT, antibodies for their immunodetection have been developed. Peptide antigens derived from sequences of selected rat sulfotransferases rSULT1A1, 1B1, 1C1, 1C2, 1C1/2, 1E1, and 2A1, were used as KLH conjugates for hen immunization to obtain yolk anti-peptide antibody (IgY). Fractions of IgY were isolated from eggs yolks by simple...
Expression of selected defects of oxidative phosphorylation system in cultivated fibroblasts
Marková, Michaela ; Hansíková, Hana (advisor) ; Kalous, Martin (referee)
AAbbssttrraacctt:: The mammalian organism is entirely dependent on ATP production by oxidative phosphorylation system (OXPHOS) on the inner mitochondrial membrane. OXPHOS is composed of respiratory chain complexes I-IV, ATP synthase and also include two electron transporters cytochrome c and coenzyme Q. Disorders of mitochondrial energy metabolism caused by OXPHOS defects are characterized by extreme heterogeneity of clinical symptoms, variability of tissues affected and the severity of the defect at the level of individual tissues. The mitochondrial disorders are not always clearly expressed at the level of available tissue or most easily available cultured fibroblasts and/or currently available methods are not capable to detect the defects on the fibroblasts level. The aim of this master thesis was to identify by biochemical methods, especially by high sensitive polarography, OXPHOS disorders in cultured fibroblasts. Cell lines from 10 patients with isolated (SURF21, SCO1 ND1, ND5) or combined defects of OXPHOS complexes whose biochemical defect was confirmed in muscle tissue as well as 14 patients with non- mitochondrial diseases (8 patients with Huntington disease, 6 patients with disorder of sulphur amino acids metabolism) were analysed. Furthermore impact of various cultivation conditions on OXPHOS...
Study of human NADH:ubiquinone oxidoreductase deficiency
Rodinová, Marie ; Hansíková, Hana (advisor) ; Kalous, Martin (referee)
NADH: ubiquinone oxidoreductase (complex I) is the most complicated enzyme of mitochondrial oxidative phosphorylation system (OXPHOS). Complex I is localised in the inner mitochondrial membrane and is composed of 45 subunits. Seven of them are coded by mtDNA, thirty eight subunits are coded by nDNA. Function of complex I is NADH oxidation and creation of proton gradient in intermembrane space by proton translocation. Mitochondrial disease caused by complex I defect are the most frequent OXPHOS disorders. Large-scale symptoms mostly affect organs with high energy demand like brain, muscle or heart. The aim of study was to characterize the impact of isolated complex I deficiency on cellular, enzymatic and protein level in patient-derived skin fibroblasts with m.3697G>A mutation in MTDN1 and c.[229C>T];[476C>A] mutations in NDUFS8. Both mutated subunits are parts of catalytic core of complex I. Heteroplasmy of mtDNA mutation m.3697G>A in fibroblast cells reached more than 90 %. Mitochondrial ultrastructure was disrupted in both patients compared to control. Mitochondrial network was nonhomogenous, mitochondrial ultrastructure showeed low cristae level and content of reactive oxygen species in both patients was significantly increased in comparison with control. Catalytic activity and protein level of...
Study of the composition and organization of cytochrome P450 system by covalent crosslinking
Koberová, Monika ; Hodek, Petr (advisor) ; Hansíková, Hana (referee)
The system of mixed function oxygenase (MFO system) participates in significant roles in the metabolism of endogenous compounds and xenobiotics. This system contains cytochrome P450, NADPH:cytochrome P450 reductase, and also there are assigned NADH: cytochrome b5 reductase and cytochrome b5. It was proved that cytochrome b5 can stimulate or inhibit cytochrome P450 (CYP)-dependent reactions and even change the ratio of resulting metabolites. The mechanism of cytochrome b5 action has not been fully elucidated yet. Elucidation of protein-protein interactions in MFO system and determination of topology of this system could explain the mechanism of cyt b5 action. The covalent cross- linking technique is suitable method for identifying protein-protein interactions within the membrane. Cytochrome b5 contains 3 methionines and in 2 cases the methionines are localized in a short hydrophobic C-terminal membrane anchor. Interactions with cytochrome P450 in the membrane environment can be identified by substitution of two methionine for photoactivatable analogue of methionine (photo-methionine) and subsequent photoactivation. This work is focused on expression and isolation of photo-cytochrome b5 (photo- cyt b5), cytochrome b5 analogue with incorporated photo-methionine. Conditions for photo-methionine...
Fumarate hydratase as tumor suppressor
Kedrová, Kateřina ; Hansíková, Hana (advisor) ; Befekadu, Asfaw (referee)
1 Abstract Fumarate hydratase (fumarase, EC 4.2.1.2) 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...
Role of chemopreventive compounds and food additives in the process of metabolism and activation of carcinogens by cytochromes P450
Fousová, Petra ; Hodek, Petr (advisor) ; Hansíková, Hana (referee)
The origin of malignant tumors have different internal and external factors and also have been shown that, for majority of exogenous chemical carcinogens, the genotoxicity depends on metabolic activation through enzymes. Members of the subfamilies CYP1A are involved in activation of precarcinogens, for example the heterocyclic amine PhIP. One of the main approaches to achieve a reduction in a cancer risk is prevention. Recently, the consumption of dietary supplements containing various chemopreventive substances, such as flavonoids, has expanded. On the other hand, some negative effects of these compounds were also confirmed, especially their ability to induce cytochrome P450 and thus increase the risk of activating precarcinogens. In this study, the inductive effect of a single administration of chemopreventive compounds, namely the effect of -naphtoflavon to cytochrome P450, had been investigated. Furthermore, a sequential study was carried out. In this study rats were first given an inducer, the -naphtoflavon, and after a passed interval they were given the carcinogen PhIP. Finally, the effect of PhIP on the activity of cytochrome P450 has been studied in vitro. KEY WORDS: cytochrome P450, carcinogens, chemopreventive compounds

National Repository of Grey Literature : 38 records found   beginprevious24 - 33next  jump to record:
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1 Hansíková, H.
1 Hansíková, Hana
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