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Effect of ectopic synthesis of mitochondrial uncoupling protein 1 in white adipose tissue on whole-body metabolism in mice
Janovská, Petra ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Kalous, Martin (referee)
The prevention and treatment of obesity is a major problem of health care systems in affluent societies. Metabolism of adipose tissue belongs to the therapeutical targets, since accumulation of adipose tissue is the basis of obesity development. Experiments using transgenic mice with ectopic expression of brown- fat uncoupling protein 1 (UCP1) in white adipose tissue (WAT), verified a concept that obesity could be ameliorated by increasing energy expenditure in WAT. The goal of the experiments of this PhD Thesis was to characterize in detail the phenotype of this unique animal model of obesity resistance. We have shown that mitochondrial uncoupling in WAT resulted in increased oxidation of fatty acids (FA), in face of decreased lipogenesis and induced mitochondrial biogenesis in this tissue. In further studies, we aimed to modulate propensity to obesity be increasing FA oxidation in WAT in response to physiological stimuli. This could be accomplished in response to the combination treatment using n-3 polyunsaturated fatty acids (n-3 PUFA) and mild calorie restriction in mice fed high-fat diet. Synergistic induction of mitochondrial oxidative capacity and lipid catabolism in epididymal WAT was associated with suppression of low-grade inflammation of WAT, which is typical for obesity. The improvement of lipid...
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Soil microbial communities in agroecosystems and natural habitats contributing to resistance and resilience of the soil environment
Sarikhani, Ensyeh ; Kopecký, Jan (advisor) ; Demnerová, Kateřina (referee) ; Větrovský, Tomáš (referee)
Ensyeh Sarikhani Soil microbial communities in agroecosystems and natural habitats contributing to resistance and resilience of the soil environment. Summary The control of common scab of potatoes (CS) includes resistant varieties (cultivars), precise fertilization, increase of soil moisture, and chemical treatments. Yet, these management practices do not have common or reproducible results at differing sites. A monitoring study was done in 32 sites to evaluate the relation between CS and biological/chemical soil parameters. Correlations were observed between scab severity and content of nutrients such as Fe, N, and Ca in soil and periderm, and between disease severity and abundance of actinobacteria and total bacteria, together with the pathogenicity determinant, txtB gene (biosynthetic gene of thaxtomin) in both soil and periderm of potatoes. The findings led to novel conclusions, which can help to understand relationships applicable in scab control. Peat and DTPA chelated iron were supplemented to pots filled with soil conducive for CS in order to determine the effects of soil organic matter, iron and pH on CS development. The results were compared with data obtained for a suppressive soil from a nearby field with naturally low CS severity. Both peat and iron supplements decreased CS and the combination...
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Changes in cell immune parameterswith focus on NK cells in patients with pancreatic cancer in relation to therapy and depression
Kopecký, Jindřich ; Filip, Stanislav (advisor) ; Vávrová, Jiřina (referee) ; Ćwiertka, Karel (referee)
Changes in cell immune parameters with focus on NK cells in patients with pancreatic cancer in relation to therapy and depression Pancreatic cancer (further PC) is one of the diseases with the greatest malignant potential. Most of patients die within 1 year from diagnosis, and only 2-5 % of patients survive more than 5 years. A major cause of late diagnosis of PC and so his insufficient therapeutic management is due to the late clinical signs of PC. Despite of progress in understanding of the molecular and biological basis of tumor genesis, the prognosis of patients with PC stays during the years unchanged. One of the often clinical signs related with PC is the presence of depressive symptoms or already developed clinically depression. The association of depression and cancer constitutes an important factor affecting the quality of life and can lead to increased morbidity. Even when the relationship between the function of subcortical centers of the brain, immune and endocrine system is known, the role of long-term stress and depression in the homeostasis is often overlooked. The mental health has a great importance for the proper functioning of the immune system from the long term. During the tumor genesis there are activated cytotoxic cells (cytotoxic T lymphocytes and NK cells) and other cell...
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Role of protein kinase C isoforms in cardioprotective mechanism of chronic hypoxia
Hlaváčková, Markéta ; Novák, František (advisor) ; Kopecký, Jan (referee) ; Novotný, Jiří (referee)
Cardiovascular diseases, particularly acute myocardial infarction, are one of the leading causes of death in developed countries. It is well known that adaptation to chronic intermittent hypobaric hypoxia (IHH) confers long-lasting cardiac protection against acute ischemia/reperfusion injury. Protein kinase C (PKC) appears to play a role in its cardioprotective mechanism since the administration of general PKC inhibitor completely abolished the improvement of ischemic tolerance in IHH hearts. However, the involvement of individual PKC isoforms remains unclear. Therefore, the primary aim of this study was to investigate the potential involvement of PKCδ and PKCε, the most prevalent PKC isoforms in rat heart, in the mechanism of IHH-induced cardioprotection. We showed that IHH up- regulated PKCδ protein in left ventricle, enhanced its phosphorylation on Ser643 and increased its co-localization with markers of mitochondrial and sarcolemmal membranes. PKCδ subcellular redistribution induced by IHH as well as the infarct size-limiting effect of IHH was reversed by acute treatment with PKCδ inhibitor rottlerin. These data support the view that PKCδ plays a significant role in IHH-induced cardioprotection. On the other hand, adaptation to IHH decreased the PKCε total protein level without affecting its...
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Development of a new sand fly exposure test to evaluate vector control tools
Willen, Laura Adrienne André ; Volf, Petr (advisor) ; Kopecký, Jan (referee) ; Valenzuela, Jesus G. (referee)
In the Mediterranean basin, human visceral leishmaniasis caused by the protozoan parasite Leishmania infantum is a zoonotic disease that gives rise to 1,200 to 2,000 new cases annually. The domestic dog constitutes its main reservoir, of which some may suffer from a severe chronic disease, canine leishmaniasis (CanL). The sand fly Phlebotomus perniciosus is considered to be the principle vector. Saliva of bloodfeeding vectors of diseases has been used in the past to assess host exposure to vector bites and to evaluate vector control tools. This Ph.D. focused on saliva of P. perniciosus to identify exposure markers that could be used in the preparation of a new vector exposure tool. The first part of this Ph.D. aimed at validating the use of a recombinant salivary protein of P. perniciosus - rSP03B - in endemic settings of CanL. During a cross-sectional study, no significant differences between the antibody (Ab) response against whole saliva or the rSP03B were observed between different regions across the Mediterranean basin. Furthermore, the rSP03B was shown to resemble the native protein. During a subsequent study this protein was used to assess the seasonal dynamics of the canine Ab response to P. perniciosus in an endemic area of L. infantum. This study elucidated that also in a heterogeneous...
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Antibiotic rezistance genes in soil actinobacteria
Patrmanová, Tereza ; Kopecký, Jan (advisor) ; Lichá, Irena (referee)
Actinobacteria are important members of the soil ecosystems, where they are involved in organic matter decomposition. It is worth mentioning that their secondary metabolism allows them to produce a variety of different compounds. These compounds include antibiotics, among them aminoglycosides have a place in clinical practice. These antibiotics are significant due to a broad spectrum of activities against both gram-negative and gram-positive bacteria. However, their use currently carries a risk, mainly their toxicity and development of antibiotic resistance in bacteria. Resistance is the cause of low effectiveness of some of those antibiotics. Actinobacteria as aminoglycoside producers must protect themselves from these compounds, so a variety of resistance types was developed, out of which enzymatic inactivation is the most studied one. Actinobacteria have evolved several mechanisms, which contribute to a resistance to the agents with antimicrobial effects. Genes encoding antibiotic resistance are abundant in soil environment. Their variability is influenced by many factors, especially the selection of bacteria in soil contaminated with antibiotics and also with strains originating from human and animal waste. Significant role has a horizontal gene transfer, which allows distribution of resistence...
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