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The role of posttranslational modifications in the molecular mechanism of the circadian clock
Janáčová, Klára ; Sumová, Alena (advisor) ; Sládek, Martin (referee)
The timing of the biological processes of organism is controlled by an endogenous circadian clock. The molecular clock is present in almost every cell and is synchronized with the external environment. The main mechanism of the clock is a transcription-translation feedback loop. The 24-hour circadian rhythm period is provided by reversible posttranslational modifications (PTMs) of the clock proteins and another regulators of the circadian clock. PTMs are further important for clock entrainment, their regulation by metabolic state in the cell, and reciprocal regulation of the circadian clock end cell cycle. Phosphorylation, histones PTMs, acetylation, SUMOylation, ubiquitination, O-linked N-acetylglucosamination and polyADP-ribosylation play a crucial role. The molecular mechanism of the biological clock is an evolutionarily conserved mechanism found in most organisms. This bachelor thesis summarizes the knowledge about the role of PTMs in the molecular mechanism of the mammalian and human circadian clocks. Key words: circadian clock, clock genes, clock proteins, posttranslational modifications
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Synchronization of circadian clock in rat during ontogenesis and in adulthood
Olejníková, Lucie ; Sumová, Alena (advisor) ; Šlamberová, Romana (referee) ; Mareš, Jan (referee)
The circadian system temporally controls behavioral and physiological processes in most organisms so that they change during the day and night with a period of about 24 h. It is an evolutionary adaptation to anticipate periodic changes in environment on the Earth. In mammals, the circadian system consists of the central pacemaker in the suprachiasmatic nuclei (SCN) of hypothalamus and of oscillators located in numerous peripheral organs and tissues. At the molecular level, the circadian clock is based on the rhythmic expression of so called clock genes. The ontogenetic development of the circadian system is a gradual process and the most important changes undergo during the late embryonic and early postnatal stage. Many behavioral, hormonal and metabolic signals provided by the mother are considered to be involved in circadian clock synchronization during early ontogenesis. The mechanisms of the entrainment are not fully known yet. The aim of this thesis was to study the development of the circadian clock and its entrainment via maternal signals and to compare the development of circadian rhythms in two model rat strains - Wistar rat and spontaneously hypertensive rat (SHR). Firstly, we described the ontogenetic maturation of the Wistar rat circadian clock in the colon from the fetal stage until...
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Entrainment of the circadian system in rodents
Sosniyenko, Serhiy ; Sumová, Alena (advisor) ; Mareš, Jan (referee) ; Šauman, Ivo (referee)
The circadian clock located within the suprachiasmatic nuclei (SCN) of the hypothalamus responds to changes in the duration of day length, i.e. photoperiod, differently in the separate SCN parts. The aim of the study was i) to compare the effect of a long and a short photoperiod with twilight relative to that with rectangular light-to-dark transition on the daily profiles of clock gene expression and their protein levels within the rostral, middle and caudal regions of the mouse SCN; ii) to elucidate the dynamics of adjustment to a change of a long photoperiod to a short photoperiod of clock gene expression rhythms in the mouse SCN and in the peripheral clock in the liver, as well as of the locomotor activity rhythm; iii) to elucidate whether and how swiftly the immature rat fetal and neonatal molecular SCN clocks can be reset by maternal cues and iv) to reveal when and where within the rat SCN the photic sensitivity of clock gene expression develops during the early postnatal ontogenesis and to compare it with development of cfos photoinduction. Mice and rats were used for experiments; their tissues were analyzed by in situ hynridization, immunohistochemistry, RT-PCR. The data indicated that i) the twilight photoperiod provides stronger synchronization among the individual SCN cell subpopulations than the...
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Development of photic entrainment of the circadian clock of the rat during early postnatal ontogenesis
Matějů, Kristýna ; Sumová, Alena (advisor) ; Höschl, Cyril (referee) ; Langmeier, Miloš (referee) ; Nevšímalová, Soňa (referee)
In most organisms, behavioral and physiological events oscillate with period ± 24 h, i.e. exhibit circadian rhythms. In mammals, circadian rhythms are generated by circadian clock within the suprachiasmatic nuclei of the hypothalamus (SCN). Light entrains circadian rhythms to the 24 h period of solar day. Information about light is conveyed from the retina to the SCN and induces expression of clock genes Period1 (Per1) and Period2 (Per2) that represent photosensitive parts of molecular circadian clockwork within SCN. Light sensitivity of Per1 and Per2 within SCN is temporally restricted to the subjective night phase. In addition, daily profiles of clock gene expression within SCN are modulated by daylenght, i. e. the photoperiod. The aim of our study was to elucidate how the mechanism of photic entrainment of the rat circadian clock develops during prenatal and early postnatal ontogenesis. Our results demonstrate that maternal circadian system provides information about external light to the fetal and early postnatal circadian clock. Circadian clock within the SCN of rat pups is light sensitive already at the first postnatal day. Mechanism gating the light sensitivity is present at postnatal day 3 and gradually maturates until postnatal day 10. The data suggest that the developing retina is responsive to...
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Significance of the timekeeping system for human health
Pospíšilová, Lucie ; Sumová, Alena (advisor) ; Hejnová, Lucie (referee)
The circadian system evolved as an adaptation to cyclic changes in external conditions on Earth, mainly the alternation of light and dark with a period of solar day. The rhythmic signal is generated at the cellular level and it is controlled by rhythmic expression of clock genes and their protein products. In mammals, the hypothalamic suprachiasmatic nuclei (SCN) are the principal circadian oscillator coordinating daily cycles of physiology and behavior, while in peripheral tissues local oscillators operate. The peripheral oscillators are entrained to the daytime and also among each other, by neuroendocrine signals from the SCN. Mutual synchrony of all the circadian components is necessary for proper function of the organism. The main entraining cue of the circadian system with environment is light, which affect the SCN via retina. In a subgroup of blind people sensing the light in the retina is disturbed and their circadian system cannot be synchronized by light. The SCN controls rhythmic production of melatonin in the pineal gland. This hormone mediates the information about the daytime to other tissues in the body, which are not photosensitive. The circadian system temporally drives many processes, including the cell division cycle. It seems that disruption of the temporal regulation could contribute to...
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Internal communication within the circadian system and its significance for our health
Honzlová, Petra ; Sumová, Alena (advisor) ; Moravcová, Simona (referee)
Mammalian circadian cycle is generated by hierarchically organized system of internal rhythmical oscillations in clock gene expression (Clock, Bmal1, Per, Cry, Rev-Erb, etc.) which take place in nearly all living cells in our body. The master pacemaker is located in suprachiasmatic nucleus (SCN) in hypothalamus. According to its synchronization to photic and non-photic external stimuli SCN generates signal for entrainment of peripheral clock. Peripheral clock synchronization is maintained via neuronal or hormonal (glucocorticoids, melatonin) pathways, regulation of body temperature or food intake and affects various physiological processes. Desynchronization of central and peripheral clock can be the cause or the manifestation of impaired health condition. Powered by TCPDF (www.tcpdf.org)
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Circadian system of SHR rats
Pačesová, Dominika ; Sumová, Alena (advisor) ; Švandová, Ivana (referee)
The suprachiasmatic nuclei (SCN) harbor the master circadian pacemaker in mammals which is responsible for control and coordination of circadian rhythms throughout the body and ensure optimal functioning of the organism in variable external conditions. The SCN is a heterogeneous structure in its morphology and function. The present thesis focuses on comparison of the SCN and its properties in an animal model of pathological hypertension, i.e. in spontaneously hypertensive rat (SHR), and nonpathological normotensive Wistar rat. To determine selected morphological and functional markers in the SCN between both rat strains, in situ hybridization and immunohistochemistry methods were used. To compare functional properties of the SCN of SHR and Wistar rat, the effect of light pulses on the expression of c-fos and Per1 genes as well as on locomotor activity were studied in both strains. Our results suggest morphological differences in the number of neurons and in the expression of Avp a Vip in the SCN with an apparent tendencies to higher levels of the studied peptides in SHR compared to Wistar rat. Our data further indicate variation in functioning of the SCN in SHR and Wistar rat on the basis of different responses to light pulses administered in the first part of the subjective night, namely in the...
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Synchronization of circadian system during prenatal and early postnatal development
Houdek, Pavel ; Sumová, Alena (advisor) ; Novotná, Růžena (referee)
One of the few attributes common to almost all living organisms is an ability to generate and maintain endogenous rhythms, which are controlled by a biological clock. The processes, which recur with a period of about 24 hours, are known as the circadian rhythms. The circadian clock controls rhythms of molecular, physiological as well as behavioral processes and adapts their activity to regularly appearing changes in day and night or season. In case of mammals, central oscillator is located in the hypothalamic suprachiasmatic nuclei (SCN). The SCN clock entrains rhythms of peripheral oscillators located in cells of other tissues. The central oscillator itself is synchronized with external environment mainly by a light-dark cycle, however, other cues can entrain the SCN clock as well. For example, during prenatal development, entrainment of a fetal clock is entirely dependent on non-photic cues derived from maternal organism. This study aimed to investigate a mechanism of the communication between the maternal and fetal central oscillators. A hypothesis was tested whether maternal melatonin may play a role in entrainment of the circadian clock in the fetal SCN. Furthermore, a mechanism, how melatonin may entrain the fetal clock was investigated at molecular level. The results provided evidence, that...
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