National Repository of Grey Literature 22 records found  1 - 10nextend  jump to record: Search took 0.01 seconds. 
Enzyme activity analysis of function domains belonging to model heme-containing sensor proteins
Prošková, Veronika ; Martínková, Markéta (advisor) ; Macek, Tomáš (referee) ; Vítek, Libor (referee)
EN This Ph.D. thesis focuses on the heme containing gas sensor proteins. These proteins are predominantly present in bacteria, in which play an important role in processes like, sporulation, antibiotic resistance and so on. Heme containing sensor proteins composed of two domains. First one is a globin domain, which contains the heme molecule. Interaction of heme with gas molecule acts as a signal for the activation/inactivation of the second functional domain. Part of this thesis is formed by a review, which summarized the current knowledge about heme containing sensor proteins. In the next part of this thesis we focused on three representatives from the group of oxygen sensor proteins - histidine kinase AfGcHK, diguanylate cyclase YddV and phosphodiesterase EcDOS. The main aim of this thesis was to solve the mechanism of interdomain/intraprotein signal transduction in two oxygen sensor proteins with globin fold of their sensor domain (AfGcHK, YddV). For this purpose, we used the kinetic analysis of their functional domain activity and the methods of structural biology. We also studied the mechanism of interprotein signal transduction in AfGcHK and its cognate partner RR protein. It was also tested, how the presence of sodium disulfide affects the functional properties of oxygen sensor proteins...
Biological effects of edible algae.
Vaňková, Kateřina ; Vítek, Libor (advisor) ; Brůha, Radan (referee) ; Mičuda, Stanislav (referee)
Nutritional factors with antioxidant properties, such as those contained in edible algae or green plants, might be implicated in protection against cancer development. Chlorophyll and other tetrapyrrolic compounds, structurally related to heme and antioxidant bile pigment bilirubin, belong to important candidate molecules, which might be responsible for these effects. Based on our studies demonstrating antiproliferative effects of S. platensis edible alga extract on experimental model of human pancreatic adenocarcinoma we investigated in detail the effect of chlorophyll occurring abundantly in this alga. Since only scarce data exist on the antiproliferative effects of chlorophylls, the aim of our study was to assess these effects. The study was performed on experimental models of human pancreatic and prostate cancer. The inhibitory effects of chlorophylls (chlorophyll a, chlorophyll b, chlorophyllin and pheophytin a) on cell proliferation and cell viability were investigated in in vitro studies. Chlorophylls reduced the mRNA expression as well as activity of hemeoxygenase in tested pancreatic cancer cells. Simultaneously, chlorophylls played an important role in redox environment of studied cancer cell lines including modulation of mitochondrial membrane potential, reactive oxygen species (ROS)...
Enzymatic and Metabolic Transformation of Silybin and its Congeners
Purchartová, Kateřina ; Křen, Vladimír (advisor) ; Macek, Tomáš (referee) ; Vítek, Libor (referee)
Natural flavonoids and flavonolignans feature beneficial properties for living organisms such as antioxidant and hepatoprotective effects, anticancer, chemoprotective, dermatoprotective and hypocholesterolemic activities. Their metabolism in mammals is complex, the exact structure of their metabolites still remains partly unclear and the standards are usually not commercially available. Hence, this project focused on the preparation of potential and defined biotransformation Phase II sulfated metabolites of silymarin flavonolignans: silybin, 2,3-dehydrosilybin, isosilybin, silychristin, silydianin and flavonoids quercetin, taxifolin, rutin and isoquercitrin. Pure sulfated derivatives were prepared using aryl sulfotransferase from Desulfitobacterium hafniense and aryl sulfotransferase from rat liver. Using heterologously expressed PAPS (3'-phosphoadenosine-5'-phosophosulfate) - independent arylsulfotransferase from Desulfitobacterium hafniense and cheap p-nitrophenyl sulfate as sulfate donor, sulfated flavonolignans and flavonoids were obtained in high yields. Silymarin flavonolignans afforded exclusively monosulfates at the position C-20 (C-19 in the case of silychristin), except 2,3-dehydrosilybin that yielded also the 7,20-O-disulfated derivative. Isoquercitrin and rutin were selectively sulfated...
Targeting mitochondria to overcome resistance of breast cancer to therapy
Rohlenová, Kateřina ; Neužil, Jiří (advisor) ; Špíšek, Radek (referee) ; Vítek, Libor (referee)
(EN) Tumours are heterogeneous and consist of multiple populations of cells. The population of cells with tumour-initiating capability is known as cancer stem cells (CSC). Cells with increased stemness properties and elevated resistance to anti-cancer treatment have been shown to be highly affected upon decline of mitochondrial respiration, linking the concept of CSCs to deregulated bioenergetics. Consistently, functional electron transport chain (ETC) is crucial in tumorigenesis. Expression of HER2 oncogene, associated with resistance to treatment in breast cancer, has been connected with regulation of mitochondrial function. We therefore investigated the possibility that manipulation of mitochondrial bioenergetics via disruption of ETC eliminates the conventional therapy-resistant populations of tumour, such as CSCs and HER2high cells. We demonstrate that HER2high cells and tumours have increased complex I-driven respiration and increased assembly of respiratory supercomplexes (SC). These cells are highly sensitive to MitoTam, a novel mitochondria-targeted derivative of tamoxifen, acting as a CI inhibitor and SC disruptor. MitoTam was able to overcome resistance to tamoxifen, and to reduce the metastatic potential of HER2high cells. Higher sensitivity of HER2high cells to MitoTam is dependent on...
The biological role of the metabolic products of haem and bilirubin.
Jašprová, Jana ; Vítek, Libor (advisor) ; Farghali, Hassan (referee) ; Mičuda, Stanislav (referee)
Present work has been focused on the importance of the products of the heme catabolic pathway, in particular under conditions of unconjugated hyperbilirubinemias (neonatal jaundice and Crigler-Najjar syndrome (CNS)). The second part of the project was focused on the improvement of some pharmacological approaches used in the treatment of these diseases, as well as on studies of bilirubin products that are formed during the treatment by phototherapy (PT). Neonatal jaundice is one of the most common complications in neonates. Currently, there is no efficient pharmacotherapy and the treatment with blue light is used as a gold standard for severe neonatal jaundice. However, the absolute safety of PT has still not been confirmed. In this context, it is important to note that some neonatologists start the PT before serum bilirubin levels reach the recommended values and that patients with CNS type I (CNSI) are forced to be on life-long PT (unless undergoing liver transplantation). The focus of the present project was to study biological effects of bilirubin photoisomers (PI) in an in vitro model of the human neuroblastoma SH-SY5Y cells that are used for studies of the neuronal metabolism. In further studies performed on animal model of hyperbilirubinemic rats and mice, we investigated a suitable gene...
Antiproliferative effects of heme catabolic pathway's products
Koníčková, Renata ; Vítek, Libor (advisor) ; Haluzík, Martin (referee) ; Farghali, Hassan (referee)
Presented work is focused on heme metabolism with the main interest in bile pigments. Recent data indicate that bilirubin is not only a waste product of the heme catabolic pathway, but also emphasize its important biological impacts, including possible antiproliferative effects. Until today metabolism of bilirubin has not been completely elucidated, which has prevented detailed evaluation of its potential anticancer action. The aim of this study was to clarify some aspects of heme catabolism with respect for antiproliferative properties of its products. Based on the fact that bilirubin potently affects carcinogenesis of the intestine, we initially investigated not properly known bilirubin metabolism by intestinal bacteria. We studied bilirubin neurotoxic effects in hyperbilirubinemic Gunn rats - its distribution in the brain tissue and its degradation during pathological conditions, such as severe newborn jaundice or Crigler-Najjar syndrome. Possible approaches to improve the treatment of severe unconjugated hyperbilirubinemias, combination of the phototherapy and human albumin administration were also investigated. The main reason of these studies was the fact that mechanisms of neurotoxic effects of bilirubin are predominantly identical with those, by which bilirubin inhibits cancer cells growth....
Role of microbiota and gut inflammation in the pathogenesis of experimental colorectal cancer
Klimešová, Klára ; Tlaskalová - Hogenová, Helena (advisor) ; Vítek, Libor (referee) ; Reiniš, Milan (referee)
Mucosal surface of the gut is in continuous contact with foreign compounds derived from diet as well as from commensal or pathogenic microorganisms. Thousands of years of symbiosis resulted in tight cooperation between the host and its microbiota. Microbiota composition and metabolism actively influence host's physiological as well as pathological processes. Chronic inflammation is characterized by prolonged active inflammatory response associated with tissue damage. This status results from accumulation of defects in various factors including gut barrier functions as well as mechanisms of innate and adaptive immunity. It's commonly accepted that chronic inflammatory diseases of the gastrointestinal tract like IBD, are associated with an increased risk of CAC development. Two publications related to this thesis deal with modulatory effects of peroral administration of components of commensal bacteria or probiotics on intestinal inflammation. Using acute or chronic model of DSS-induced colitis, we demonstrated that oral treatment of BALB/c mice with membranous fraction of the commensal, Parabacteroides distasonis, as well as with lysate of probiotic bacterium Lactobacillus casei DN-114 001 significantly reduces the severity of intestinal inflammation. Moreover, the treatment was associated with reduction of...
The study of the influence of vitamin E analogues on malignant mesothelioma
Kovářová, Jaromíra ; Neužil, Jiří (advisor) ; Kozubík, Alois (referee) ; Vítek, Libor (referee)
Cancer is a leading cause of death in the western world and is increasing in frequency world-wide. Although diagnosis, treatment and therapeutic approaches to cancer have improved, many types of cancer are still lethal due to the lack of radical treatment. One of the fatal neoplastic disease types with poor prognosis is represented by malignant mesothelioma (MM). MM is characterised by very high mortality rate and limited therapeutic options. The etiology of the disease is mainly associated with exposure to asbestos fibres. The incidence of MM is increasing in many countries. The search for novel molecular targets, anti-cancer strategies and drugs, which would considerably improve the treatment is of great importance. Certain new drugs, especially those with specific molecular targets, show high selectivity in their action to cancer cells, and have considerably increased the cure rate in some types of cancer. Mitochondria have recently emerged as a very promising target for anti-cancer agents. A group of compounds with anti-cancer activity that induce apoptosis by way of mitochondrial destabilisation, termed 'mitocans', have been a recent focus of research. Several mitocans have been shown to selectively induce apoptosis in cancer cells and suppress the growth of many types of carcinomas in...

National Repository of Grey Literature : 22 records found   1 - 10nextend  jump to record:
See also: similar author names
5 VÍTEK, Libor
1 Vítek, Ladislav
3 Vítek, Leoš
10 Vítek, Lukáš
Interested in being notified about new results for this query?
Subscribe to the RSS feed.