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Molecular mechanisms of circadian clock entrainment by daily regime in food intake
Kapoun, Jiří ; Sumová, Alena (advisor) ; Červená, Kateřina (referee)
Circadian clocks form an endogenous time-keeping system present in most organisms, synchronizing physiological and behavioural processes with perodically changing environmental conditions. The system comprises of the master clock in the suprachiasmatic nuclei of the hypothalamus and numerous subsidiary clocks in peripheral tissues. Its molecular design is constituted by the clock genes, which are rhythmically expressed, form a series of transcriptional/translational feedback loops and influence the expression of various other genes involved in metabolic pathways. The peripheral clocks are dependent on the master clock, although they can be entrained with external cues like food intake timing and diet composition. This desynchronization leads to the distruption of clock gene oscillation, which can potentially have serious impact on metabolic processes and increase the risk of metabolic disorders. The aim of this thesis is to summarize current knowledge on the relationship of molecular chronobiology and nutrition with a focus on the molecular mechanisms through which can food, especially its intake timing and composition, influence the crosstalk between clock gene expression and cellular metabolism. The thesis also emphasises the potential effect of circadian clock disruption on the risk of metabolic...
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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CIrcadian regulation of miRNA and clock-controlled genes in tumorigenesis
Balounová, Kateřina ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee)
The circadian clock generates circadian rhythms, which participate on regulation of a number of signalling pathways. Disruption of the circadian regulatory mechanism is linked to a development and a progression of certain types of cancer including colorectal tumorigenesis. Progression of tumorigenesis depends on the cell cycle machinery related to cell proliferation and apoptosis. MiRNAs play a role in initiation and progression of tumorigenesis because they interfere in regulatory pathways associated with tumorigenesis. The aim of the thesis was to determinate existence of circadian rhytms in clock controlled genes (Tef, Dbp), miRNAs (miR-1-3p, miR-16-5p, miR-34a-5p, miR-155-5p, miR-192-3p) and genes of the cell cycle machinery (Ccnd1, Ccne1, Ccna1, Ccnb1) and apoptosis (Casp3, Bcl2, Bad). Further, to compare detected circadian rhythms during aging and neoplastic transformation of colon by quantitative RT-PCR. We have observed circadian expression of Tef, Dbp, Ccne1, Ccna1, Ccnb1, Casp3 and Bcl2 in young mice colon, Tef, Dbp, miR-1-3p, Ccne1, Ccna1 in old mice colon and Tef and Dbp in colorectal tumors. In summary, circadian expression of clock controlled genes varied but was maintained in mice colorectal tumors. In aging we demonstrated weakening of circadian rhythms of the genes of the cell...
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Role of intestinal circadian clock in epithelial transport, proliferation, and tumourigenesis
Soták, Matúš ; Pácha, Jiří (advisor) ; Bendová, Zdeňka (referee) ; Herichová, Iveta (referee)
AABBSSTTRRAACCTT The molecular circadian clock enables anticipation of environmental changes. In mammals, clocks are ubiquitously present in almost all tissues and they are comprised of transcriptional-translational feedback loops of the so-called clock genes. The central clock represents the intrinsic pacemaker which is located in suprachiasmatic nuclei (SCN) of hypothalamus and synchronizes peripheral clocks. Clockwork system in alimentary tract and its regulatory link to intestinal functions are poorly understood. Therefore the objective of the thesis was to characterize molecular clock in particular parts of the rat intestine and to elucidate its link to the intestinal transport, regulation of cell cycle and neoplastic transformation in colonic tissue. We used quantitative RT-PCR (qPCR) to determine circadian profiles of mRNA expression of clock genes in the epithelium of duodenum, jejunum, ileum, and colon of rat. Furthermore, we analysed the expression of genes coding sodium chloride transporters and channels as well as cell cycle regulators in colon. To focus more precisely on different structures of intestinal epithelia we used laser capture microdissection. In addition, we performed Ussing chamber measurements to determine the colonic electrogenic transport. To study the contribution of circadian...
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Circadian regulation of glucocorticoid secretion
Tejkal, Karel ; Sumová, Alena (advisor) ; Soták, Matúš (referee)
Glucocorticoids belong to a family of steroid hormones synthesized in the adrenal gland. They fulfill a variety of functions related to metabolism, immune response and ontogenesis. Glucocorticoids function as the end-effector of hypothalamic-pituitary-adrenal (HPA) axis and as such, their levels in blood are elevated after exposure to stressors. The basal levels of glucocorticoid also show a pronounced diurnal rhythm, suggesting involvement of the circadian clock in the regulation of HPA axis. Studies have shown that other regulatory mechanisms apart from the HPA axis are involved in regulation of diurnal glucocortioid secretion. The disturbances of the regulatory mechanisms may lead to serious pathological conditions. This thesis describes the rhythmic nature of glucocorticoid release and mechanisms by which the circadian clock exerts its influence over the rhythm. Thereafter, the feedback of glucocorticoids onto the clock system is briefly explained. Finally, some examples of a role of abnormal glucocorticoid secretion in selected pathologies are provided.
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Molecular and environmental factors connected to diapause and aging in insect
ZDECHOVANOVÁ, Lenka
Current models state that insect peripheral oscillators are directly responsive to light, while mammalian peripheral clock genes are coordinated by a master clock in the brain via intermediate factors, possibly hormonal. We show that the expression levels of two circadian clock genes, period (per) and Par Domain Protein 1 (Pdp1) in the peripheral tisue of an insect model species are inversely affected by contrasting photoperiods. The effect of photoperiod on per and Pdp1 mRNA levels was found to be mediated by the juvenile hormone. Our results provide the first experimental evidence for hormonal regulation of circadian clock gene expression in insects.
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Cirkadiální hodiny se neúčastní načasování buněčného dělení v řase Chlamydomonas reinhardtii
Vítová, Milada ; Bišová, Kateřina ; Hendrychová, Jana ; Čížková, Mária ; Zachleder, Vilém
To determine whether the circadian clock functions in control the entry of algal cells into the cell cycle, we have tested the green alga Chlamydomonas reinhardtii in a wide range of growth conditions both light intensity and temperature. We monitored the course of the cell cycles in asynchronous as well as in synchronized cultures. The cultures were grown either at the continuous light or at alternating light/dark periods. The length of the cell cycle was monitored also at different temperatures and in “circadian” mutant. We have evidenced that the length of the cell cycle corresponding to circadian times can be attained only under relatively narrow range of growth conditions and even in this case the “circadian time” is a result of given growth conditions and not of any circadian gating. These results suggest that the intrinsic circadian clock does not play any role in timing of the cell cycle division in the green alga Chlamydomonas
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