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The role of SGIP1 protein interaction with cannabinoid receptor 1 in nociception under pathological conditions.
Dresslerová, Denisa ; Špicarová, Diana (advisor) ; Zímová, Lucie (referee)
The cannabinoid receptor type 1 (CB1) is a component of the endocannabinoid system and is abundantly expressed in the central nervous system. CB1 receptor has been extensively studied primarily due to its inhibitory role in neurotransmitter release from presynaptic terminals, and this process subsequently modulates postsynaptic currents and postsynaptic neuron excitation. Its interaction with the Src homology domain 3 growth factor 2 receptor binding protein (SGIP1) has recently been investigated in the context of nociception modulation (Hájková et al., 2016b). However, the role of this CB1 regulatory protein, SGIP1, in pathological pain conditions has not yet been described. Clarification of the role of SGIP1 interaction with CB1 receptor may help future research based on the use of cannabinoids as potential therapeutics. The thesis is structured into two parts, theoretical and practical. In the theoretical part of the thesis, knowledge of the given topic is summarized. First, pain is described from an anatomical-physiological perspective, followed by a description of the endocannabinoid system, where a part is dedicated to the CB1 cannabinoid receptor itself, and then another part is dedicated to the SGIP1 protein and its interaction with the CB1 receptor. In the practical part, the role of SGIP1...
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The impact of post-translational modifications on TRPC5 ion channel activation and modulation
Mitro, Michal ; Zímová, Lucie (advisor) ; Dolejší, Eva (referee)
Transient Receptor Potential Canonical 5 (TRPC5), a calcium-permeable ion channel, acts as a versatile receptor in sensory neurons, kidneys, and the brain, impacting inflammatory responses and various types of pain. While post-translational modifications influence TRPC5 gating and membrane trafficking, only a few have been described so far. The identification of phosphorylation sites was based on available high-throughput bioinformatics and mass spectrometry data. Subsequently, functional characterization of these sites was conducted by introducing phospho-mimicking aspartate or phospho-null alanine mutations using site-directed mutagenesis. Utilizing patch-clamp in whole-cell configuration, membrane currents evoked by voltage or agonist stimuli were examined. The results revealed that individual substitutions at the N-terminal S193 and S195 with aspartates significantly slowed the gating kinetics. Additionally, a gain-of-function phenotype was observed with S193A. Molecular dynamics simulations provided insight into how phosphorylation at S193 induces changes in interactions among neighboring subunits. Moreover, biotinylation experiments indicated that the alterations in the activity of the S193 mutations are not due to increased targeting of the channels to the plasma membrane. Taken together,...
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The role of TRP ion channels in rheumatoid arthritis pain
Havrilčáková, Gabriela ; Zímová, Lucie (advisor) ; Heleš, Mário (referee)
Rheumatoid arthritis is a disease that affects many people across the world. It is a chronic autoimune disease causing inflammation in joints. The inflammation affects joint lining and causes gradual damage to the joint cartilage. Main symptoms are swelling and pain, The perception of pain is closely related to a group of TRP receptors expressed on sensory neurons. The state of inflammation in the affected joints also has a significant influence on the pain accopanying rheumatoid arthritis, in which participate the cells of the joint lining - synovial fibroblasts. They express a subset of TRP receptors that play a key role in the pathophysiology of arthritis development as well. In relation to pain and inflammation, the most studied TRP receptors are TRPV1 and TRPA1. This bachelor thesis describes the findings on these two receptors in relation to pain in rheumatoid arthritis. However, it also describes the TRPC5 receptor, whose inhibiton has only recently been shown in a mouse model to leads to exacerbation of symptoms. The results discussed in this bachelor's thesis show, that pharmacological modulation of the activity of TRP receptors is a promising way of possible future treatment of rheumatoid arthritis, including its main symptom - pain. Key words: rheumatoid arthritis, transient receptor...
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Fight for Naked Life in Lustig's Presentation of Holocaust
Zimová, Lucie ; Peterka, Josef (advisor) ; Kubíček, Tomáš (referee)
This essay deals with the problems of Lustig's characters they without their real cause have to be commited the danger of the closeness to death. For understanding the choice and classification of the characters it is necessary the consequent face-off the biographical texts. A brief autobiography is indicated in the first chapter and then runs through the all other chapters (the biographic parts are in italics). The second chapter deals with the possibility of presentation of Holocaust in general and delimits the Lustig's opinion to this problems. My work treat of characters they found themselves in the threshold of sink or swim and they are obliged to fight for their dear life. Each of them chose other strategy how to approach a fight for naked life. This study divides the characters into four typological categories. To each of this category is devote one chapter with the brief presentation of the problems with several characters they correspond to this typology. First of them deals with the persons they fight against death by the act whether tragic defiance or revenge is concerned. Into this category the characters from following stories were put : Modravé plameny (Bluish Blaze), Dívka s jizvou (The Girl with the Scar), Nemilovaná (Not Beloved), Tma nemá stín (Darkness Casts no Shadow), Modlitba pro...
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Reader - response strategy of Lustig's texts
Zimová, Lucie ; Kubíček, Tomáš (advisor) ; Peterka, Josef (referee)
Dissertation deals with reader-response strategies of some Lustig's texts. Our aim is to prove if Lustig relies on high subject and culture encyclopedia of his readers or if his works have esthetic value without these requirements. First part of this dissertation is devoted to the theory of reader-response esthetic. We shortly present the main terms and representatives of this concept. In analysis of this works we concentrate us on the story as an interaction of the process, narration, figures and of the space because these levels are the most substantial part for the work response. Dissertation is always divided into theoretic part which introduces us with the solution for the next analysis and into practical part where we within our scope try to interpret the used strategies. In the chapter "Narration" we mainly focus us on narrator and his possible unreliability further on the speech form and the telling order and speed. In the chapter "Figure as a text phenomenon" we are mainly interested in figure condition and the process of its imaging. Finally in the chapter "Space and its functionality" we are concerned with the problem how Lustig manages (does not) to display functional space without relying on culture encyclopedia of his readers. This show us that Lustig calculates with response horizon and thus...
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Relationship between the parents of pre-scholars to the children book
Zelinská, Barbora ; Hník, Ondřej (advisor) ; Zimová, Lucie (referee)
This thesis deals with pre-reading literacy and focuses on the factors and actors that it develops. The first chapter deals with the theoretical definition and importance of education to the reading. The second chapter outlines the literary form of preschool education and how the literary education is included in the general educational program for preschool education. The third chapter is devoted to the primary and most important factor that the development of a child's reading act, and that is the family. It shows the possibilities of how children can relate to the books in the family to support the role of the relationship of their parents to read and stresses the importance of reading and storytelling in the family circle. The following chapter deals with the cooperation of nursery school and family in the development of a child's reading, closer is about the influence of teacher's personality and it offers opportunities to work with the book in full day kindergarten regime. The last two chapters of the theoretical part characterizes the specifics of children's literature and provide an overview of the typology of literature for preschool children. The research part describes the process of investigation, which is aimed at determining the important criteria in the selection of children's books....
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The role of charged residues in the activation and modulation of the TRPA1 ion channel
Zímová, Lucie ; Vlachová, Viktorie (advisor) ; Doležal, Vladimír (referee) ; Rokyta, Richard (referee)
Important receptor for sensing painful stimuli is ion channel TRPA1, which is expressed in peripheral endings of nociceptive neurons, where it serves as transducer of physical and chemical environmental signals to the language of the nervous system. The effort to understand the mechanisms of its activity on a molecular level is driven by the vision of progress in treatment of chronic pain in humans. Our work focused on C-terminal cytoplasmic domain of TRPA1 receptor, where we described i.a. the probable binding site for calcium, which is the most important TRPA1 modulator. Using the combination of homology modeling and molecular dynamic simulations with electrophysiological measurements we were able to explain molecular basis of familial pain syndrome caused by TRPA1 point mutation. We contributed to the understanding of the TRPA1 voltage-dependent activation mechanism by describing the amino acids in proximal C-terminus and in S4-S5 linker of transmembrane domain that are directly involved in voltage-dependent gating. Powered by TCPDF (www.tcpdf.org)
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