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Adenosine signaling: the role in neuroprotection and neurodegeneration
Hrušovská, Kateřina ; Novotný, Jiří (advisor) ; Kolář, David (referee)
The aim of this bachelor thesis is to describe basic and the most important mechanisms of adenosine signaling, especially in the central nervous system, where the purine nucleoside adenosine plays important role like significant neuromodulator. Strong release of adenosine to extracellular space may occur under some pathological conditions. Adenosine works throught his four receptors, which have very diverse functions. Some effects are neuroprotective - these are predominantly mediated throught the inhibitory A1 receptor, which can reduce neurotoxicity, others may also induce neurodegeneration, mainly due to increased activation of A2A receptors. This signaling system can be diversely modulated, for example by inhibition of enzymes, which can provide adenosine formation or degradation, blocking its transporters, by agonists or adenosine antagonists, or by inhibition of second messengers and various protein kinases by which adenosine affects cellular processes. Interactions of adenosine receptors with other types of receptors in the brain are also important. Adenosine and adenosine receptors can participate in neurodegenerative processes. A detailed understanding of the specific effects of adenosine can bring great progress in the treatment of neurodegenerative diseases. At present, intensive...
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Adenosin a nádorová imunoterapie
FREJLACHOVÁ, Andrea
The aim of this bachelor thesis was to study the immunosuppressive effects of adenosine and the use this knowledges in cancer immunotherapy. The impact of enzymatic removal of adenosine on efficacy of cancer immunotherapy was examined using murine pancreatic model Panc02.
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Úloha adipokinetického hormonu v metabolismu základních živin u octomilky obecné \kur{Drosophila melanogaster}
KUTHANOVÁ, Michaela
The aim of the thesis was evaluation of various metabolic characteristics in the fruit flies Drosophila melanogaster with deficiency of adipokinetic hormone (AKH) production, and with adenosine receptor dysfunction. The experiments were done with a goal to evaluate involment of AKH and adenosine into control of the metabolic pathways. For that measuring of basic nutrients, level of Drome-AKH, mortality and some others characteristics in the fruit flies during starvation were performed. Results revealed the effect of AKH on metabolism of storage nutrients, however, the role of adenosine was unclear.
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Přítomnost nízkomolekulárních imunomodulátorů ve slinách klíštěte \kur{Ixodes ricinus}
HAUSEROVÁ, Simona
Ticks use proteinaceous molecules contained in their saliva to suppress immune response of the host to complete their succesful feeding. In some ticks (e.g. Rhipicephalus sanguineus) presence of non-proteinaceous molecules was discovered. The aim of this work was to determine the amount of these molecules in the saliva of Ixodes ricinus tick. Namely, prostaglandin E2 and adenosine were analyzed. The second aim of this work was to evaluate the role of both low molecular weight components (or at least one of them) in the suppression of TNF-alfa cytokine production in suitable cells by ticks saliva.
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Nádorová imunoterapie a možnosti zesílení jejího účinku
KVARDOVÁ, Karolína
The aim of this thesis was to study cancer immunotherapy based on combination of TLR7 signalling and activation of phagocytosis of cancer cells. This thesis was focused on the possibility of enhancing its effect. The possibilities of removing immunosuppressive barriers (esp. MDSCs and adenosine) were studied, using a combination with chemotherapy or enzyme - adenosine deaminase and purine nucleoside phosphorylase. The effect of enzymes was studied in both in vivo and in vitro experiments. As another way of optimizing the therapy used so far, the modulation of the therapeutic mixture using lower molecular weight substances was tried.
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Microglia control adenosine A2A-receptor mediated astrogliosis
Svobodová, Magdaléna ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Magdaléna Svobodová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Assoc. Prof. Maria da Glória Correia da Silva Queiroz, Ph.D. Title of diploma thesis: Microglia control adenosine A2A-receptor mediated astrogliosis In the central nervous system, astrocytes and microglia are the main cells coordinating the inflammatory response. During inflammation, dying or temporarily damaged cells release ATP, as a danger-associated signal molecule, that contributes to the induction of astrogliosis and promotes clearance of the debris by immune cells such as microglia. Adenosine that results from ATP metabolism also stimulates astrogliosis. However, the effects of adenosine on astrogliosis may be more complex, since it also modulates microglia phenotype and microglia have been shown to prevent excessive astroglial proliferation mediated by nucleotides. In this context, ATP and adenosine are assumed as relevant signalling molecules in the control of astrogliosis and its modulation by microglia. However, it is still unknown whether and how microglia modulate adenosine-mediated astrogliosis. The present study aims to clarify the impact of microglia in the control of adenosine-induced astrogliosis. Two...
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Microglia control adenosine A2A-receptor mediated astrogliosis
Svobodová, Magdaléna ; Mladěnka, Přemysl (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Magdaléna Svobodová Supervisor: Assoc. Prof. Přemysl Mladěnka, Ph.D. Assoc. Prof. Maria da Glória Correia da Silva Queiroz, Ph.D. Title of diploma thesis: Microglia control adenosine A2A-receptor mediated astrogliosis In the central nervous system, astrocytes and microglia are the main cells coordinating the inflammatory response. During inflammation, dying or temporarily damaged cells release ATP, as a danger-associated signal molecule, that contributes to the induction of astrogliosis and promotes clearance of the debris by immune cells such as microglia. Adenosine that results from ATP metabolism also stimulates astrogliosis. However, the effects of adenosine on astrogliosis may be more complex, since it also modulates microglia phenotype and microglia have been shown to prevent excessive astroglial proliferation mediated by nucleotides. In this context, ATP and adenosine are assumed as relevant signalling molecules in the control of astrogliosis and its modulation by microglia. However, it is still unknown whether and how microglia modulate adenosine-mediated astrogliosis. The present study aims to clarify the impact of microglia in the control of adenosine-induced astrogliosis. Two...
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The anti-oxidative stress response in Drosophila malanogaster involvement of adipokinetic hormone and adenosine
Zemanová, Milada ; Kodrík, Dalibor
The anti-oxidative stress response was studied in Drosophila melanogaster larvae and adults with mutation in genes of adipokinetic hormone (Akh), and adenosine receptor (AdoR(1)), and both these genes together (Akh(1) AdoR1 double mutant). To elicit the oxidative stress we administered paraquat (PQ) in food. Mortality tests revealed the double mutant Akh(1) AdoR(1) was more sensitive to PQ toxicity than either of the single mutants. The PQ administration significantly increased the Drome-AKH hormone level in control w(1118) and AdoR(1) larvae. On the contrary, PQ significantly increased expression of glutathione S-transferase D1 (GstD1) gene. It seems that both functional adenosine receptor and AKH itself are important for the proper control of the GstD1 gene expression under oxidative stress. On the other hand, differences in glutathione S-transferase (GST) activity among the strains, and between untreated and PQ treated groups were minimal. Next, the glutathione (GSH) level was significantly lower in all untreated mutant groups as compared with untreated control w1118 flies and declined further when the flies were treated with PQ. Thus, we demonstrated the important role of AKH and adenosine in control of anti-stress response elicited by PQ in D. melanogaster model.
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Role of IDGFs and adenosine signaling in cell survival and energy homeostasis
BROŽ, Václav
Two groups of growth regulators were described in Drosophila imaginal disc cell culture Cl.8+. Imaginal disc growth factors (IDGFs) belonging to chitinase-like protein family of carbohydrate binding proteins and Adenosine deaminase-related growth factors (ADGFs), which are active adenosine deaminases influencing homeostasis of key cellular metabolite adenosine. The functions of two of the IDGFs, as well as the effects of extracellular adenosine and its receptor were studied primarily in in vitro cell culture. Our results supported their roles in the regulation of cell survival and energy homeostasis especially in imaginal disc cells. Both the IDGFs and adenosine also play important roles in organismal responses to stress and infection and may interact in vivo.
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Adenosine metabolism and its role in cell physiology
Neumannová, Kateřina ; Novotný, Jiří (advisor) ; Hansíková, Jana (referee)
Adenosine is not just a major component of important molecules such as ATP, RNA or cAMP, but also has its own signaling function. Therefore, its extracellular level is strictly maintained by balance in its formation, degradation and transport. Both inside and outside the cell adenosine is formed mainly through degradation of ATP and is eliminated by two enzymes, adenosine kinase and adenosine deaminase. Transport of adenosine through the cell membrane is provided by nucleoside transporters, which are either equilibrative or concentrative according to the mechanism of transfer. All three processes described above contribute to maintaining adenosine level under normal conditions and its increase in pathological situations. Extracellular adenosine as a signal molecule binds to adenosine receptors (subtypes A1, A2A, A2B, A3) that affect many cellular signaling pathways via G-proteins. By these pathways adenosine regulates energy homeostasis, controls the function of various organs and also modulates the nervous and immune system and thus it may participate in a number of pathological processes. Pharmacological affecting of specific adenosine receptors or enzymes involved in its metabolism can serve as an effective therapy. Some drugs based on this system are already in use, others are being tested, and many...
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