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The study of mitochondrial energy-metabolism maturation
Křížová, Jana ; Hansíková, Hana (advisor) ; Pecina, Petr (referee) ; Rauchová, Hana (referee)
During intrauterine development in mammals, the fetus is exposed to a hypoxic environment. To allow proper postnatal adaptation to external conditions, a rapid transition from glycolytic to oxidative metabolism by mitochondria is required in fetal tissues after birth. Mitochondrial maturation is a complex process that is not only transcriptionally regulated. Using techniques such as microarray analysis, quantitative PCR, measurement of enzyme activities or coenzyme Q (CoQ) levels, we have described the acceleration of mitochondrial metabolism in rat liver tissue and skeletal muscle during the perinatal period and correlated the results with those in humans. Of the 1546 rat mitochondrial genes tested, we found statistically significant differences in the expression of 1119 in liver and 827 in muscle. The most significant shift in expression occurred in the rat liver between 20th and 22nd day of gestation, suggesting that the rat fetus is ready for the transition to external conditions at least 2 days before birth. Changes in CoQ levels in both rats and humans show that the amount of CoQ is low inthe prenatal period and increases after birth in both tissues. We have described the atypical kinase Coq8ap as an enzyme whose expression increases significantly after birth. It was previously predicted to...
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Combined pharmacotherapy of different types of pulmonary hypertension
Krása, Kryštof ; Hampl, Václav (advisor) ; Neckář, Jan (referee) ; Al-Hiti, Hikmet (referee)
Pulmonary hypertension is a group of diseases characterized by increased mean pulmonary artery pressure. Especially in group 2, which is associated with heart disease and is the most prevalent of all types, and in group 3, associated with lung disease, no sufficiently effective treatment has yet been developed beyond the treatment of the underlying disease, which is problematic in many cases. Dehydroepiandrosterone sulfate (DHEA S) and statins have different mechanisms of action on pulmonary hypertension in some respects, so the question of the effectiveness of combining them on pulmonary hypertension versus either agent alone has been offered. To test this hypothesis, we induced pulmonary hypertension in adult male rats by three weeks of exposure to hypoxia (10% O2) and treated them with simvastatin (60 mg/L) and DHEA S (100 mg/L) in drinking water, either alone or in combination. Both simvastatin and DHEA S reduced mean pulmonary artery pressure (from a mean ± s.d. value of 34.4 ± 4.4 to 27.6 ± 5.9 and 26.7 ± 4.8 mmHg, respectively), but their combination was not more effective (26.7 ± 7.9 mmHg). Differences in the degree of oxidative stress (as indicated by malondialdehydedehydplasma concentration), the degree of superoxide production (electron paramagnetic resonance) or blood nitric oxide...
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The effect of long-term morphine and its withdrawal on selected signaling proteins in rat heart
Ilková, Karolina ; Novotný, Jiří (advisor) ; Černá, Věra (referee)
Morphine is considered the gold standard among analgesics in the treatment of severe pain due to its effects mediated by μ-opioid receptors. However, it also produces various side effects and poses a high risk of developing tolerance and dependence. The aim of this bachelor thesis is to contribute to the elucidation of the action of morphine at the molecular level in cardiac muscle. Changes of protein levels in key signaling molecules in the signaling cascade induced by morphine administration with increasing doses and subsequent abstinence for 24 hours, 1 month and 3 months were investigated. Specifically, these were adenosine A2b receptor, β2-adrenergic receptor, κ-opioid receptor, G protein subunits, GRK5 kinase, and β-arrestin 2. Data of changes in expression were obtained from cardiac tissue homogenates (left ventricle) by Western blot followed by immunodetection, captured on light-sensitive photofilms, and statistically evaluated by ANOVA. Morphine administration did not lead to statistically significant changes in G protein subunits, β- arrestin 2, GRK5 kinase, adenosine A2b receptor, β2-adrenergic receptor, or κ-opioid receptor in rat heart. Therefore in order to develop better and safer analgesics, there is a high necessity of understanding the underlying molecular mechanisms of morphine...
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The role of protein kinase C in cardioprotection elicited by mild cold acclimation
Lážnovská, Lucie ; Žurmanová, Jitka (advisor) ; Hlaváčková, Markéta (referee)
This master's thesis examines the role of protein kinase C (PKC) in cardioprotection induced by mild cold. PKC is a crucial signaling transduction enzyme that regulates cell growth, differentiation, and survival of the cell. Mild cold, as a novel potential therapeutic strategy, protects tissues from ischemic damage. Studies by Yang et al. suggest that hypothermia activates PKC in cardiomyocytes, triggering a cascade of signaling pathways with protective effects. PKC phosphorylates and activates proteins crucial for cell survival and recovery after ischemia, while also inhibiting apoptosis and limiting the formation of reactive oxygen species that contribute to cell damage during ischemia and reperfusion injury. This work focuses on understanding the molecular mechanisms and signaling pathways associated with the role of PKCε and δ isoforms in cardioprotection induced by mild cold, which could contribute to the development of new therapeutic strategies protecting the heart from ischemic damage. Keywords: protein kinase C, PKCε, PKCδ, mild cold, cardioprotection
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The influence of creatine kinase system during the development of a cardioprotective phenotype in a rat adapted to a mild cold
Dzobová, Tereza ; Žurmanová, Jitka (advisor) ; Alánová, Petra (referee)
Cardiovascular diseases are still one of the most common causes of death and impaired quality of life worldwide. This is the reason why more and more researches start to focus on the possible prevention and treatment. One of the possible interventions that could help in this field is a relatively new model of a mild cold adaptation, first introduced in our laboratory, where the cardioprotective effects have already been proven as they reduced the magnitude of an ischemia-reperfusion damage without any negative side effects. One of the studied areas of the myocardium is the creatine kinase system, which represents a dynamic intracellular system of numerous isoenzymes stored specifically in the places of energy production and consumption. Its primary function lies in a cardiac energy metabolism and in an overall energy homeostasis in muscles, brain and other organs with high and rapidly changing demands for an energy supply. However, the molecular basis of these metabolic processes and their course induced by a cold adaptation are not yet fully known. Therefore, the aim of this work was to determine the changes in expression of three CK isoforms (CKB, CKM, mtCKs) after exposure to a mild cold (8±1 řC) during the period of an acute cold (1, 3, 10 days) and during the period of a chronic cold (5 weeks)...
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The role of centrobin in spermatogenesis
Flintová, Jennifer ; Komrsková, Kateřina (advisor) ; Šebková, Nataša (referee)
Spermatogenesis is a highly orchestrated, strictly regulated cascade of events that could be divided into three major processes: mitotic expansion of diploid germ cells (spermatocytogenesis), meiotic division creating haploid cells, and spermiogenesis. Spermiogenesis, the final stage of spermatogenesis comprises a striking metamorphosis of round haploid spermatids into morphologically and functionally specialized spermatozoa designed for the fertilization. One of the proteins indispensable for proper sperm morphogenesis is centrobin, a structural component of the specialized cytoskeletal structures of the elongating spermatids (acroplaxome and manchette), executing essential role in sperm head shaping and assembly of the head-tail coupling apparatus. Disruption in Cntrob gene (coding for centrobin) in rats homozygous at the hd (hypodactyly) locus results in male infertility, with a striking morphological signature called "decapitated sperm syndrome" with detachment of sperm head from the flagellum due to impaired head-tail coupling. However, molecular function of centrobin in spermiogenesis is still unknown. Sperm decapitation is a distinct phenotype described in several mouse mutants and importantly from infertile human males. Strikingly, in addition to proteins functioning in cytoskeletal...
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Nutrigenetic analysis of metabolic syndrome: the role of spontaneously hypertensive rat chromosome 4
Petrů, Karolína ; Šeda, Ondřej (advisor) ; Malínská, Hana (referee)
Metabolic syndrome (MetS) is a complex condition with a number of interacting genes, epigenetic and environmental factors underlying its pathogenesis. The analysis of genetic component of MetS showed that number of defining parameters of the syndrome is linked to regions of rat chromosome 4. In order to verify these quantitative trait loci (QTL), a double congenic strain was derived with parts of chromosome 4 of spontaneously hypertensive rat (SHR, an inbred MetS model) origin introgressed onto genomic background of congenic Brown Norway strain (BN-Lx). The aim of the proposed thesis is comprise detail genetic mapping of differential segments of the above mentioned double congenic strain BN-Lx.SHR4 and comparison of its metabolic profile under different dietary conditions with varying carbohydrate and fat content. Utilizing DNA sequence and gene expression comparisons, candidate genes or polymorphisms for the MetS aspects and potential nutrigenetic interactions will be identified. Key words: nutrigenetics, experimental models, metabolic syndrome, congenic strain, genotyping, rat
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Cardioprotective action of remote ischemic perconditioning in rats
Chalupová, Miloslava ; Neckář, Jan (advisor) ; Žaloudíková, Marie (referee)
Remote ischemic perconditioning (RIPerC) stimulated by brief nonlethal periods of ischemia and reperfusion of a remote organ or a tissue applied during myocardial infarction, is a powerful cardioprotective maneuver. Because of its easy realization, for example, through inflation and deflation of blood pressure cuff, this method has a big potential for translation to clinical settings. The main purpose of this thesis was to investigate the cardioprotective effect of RIPerC as a reduction of infarct size and the incidence and severity of ischemic and reperfusion arrhythmias and to examine, whether this protective effect will be confirmed also in rats with partial deletion of a transcriptional factor of hypoxia-inducible factor-1α (HIF-1α). HIF-1α is a main regulator of hypoxic intracellular signalization and its role was previously indicated in cardioprotection by local ischemic preconditioning. Anesthetized rats were subjected to 20 minutes of the left anterior descending coronary artery occlusion followed by 3 hours of reperfusion. RIPerC was performed by 3 cycles of 4 minutes of ischemia and 2 minutes of reperfusion with a pressure cuff placed on both hind-limbs. This study shows that RIPerC failed to induce protection in any observed factors of ischemia-reperfusion heart injury. Key words: heart,...
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Dopad alimentární expozice bisfenolu S na vybrané orgány laboratorních potkanů
ROČEŇOVÁ, Adéla
The present thesis investigated the impact of a ten-week oral exposure to BPS (50 ?g/kg live weight/day) in female outbred Wistar Han rats. The effect of BPS exposure on live weight, absolute and relative kidney and liver weights, morphometric parameters of kidney and renal corpuscles, histopathological changes of kidney and liver were evaluated. In addition, the concentration of total protein, triacylglycerols, cholesterol, urea and alanine aminotransferase activity were determined in blood serum.
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The effect of long-term morphine application on clock genes expression in the rat brain
Pačesová, Dominika ; Bendová, Zdeňka (advisor) ; Roubalová, Lenka (referee) ; Polidarová, Lenka (referee)
The circadian and opioid systems are systems involved in maintaining homeostasis in the body. Disruption of the circadian system disturbs the proper timing of physiological processes, which can result in the development or exacerbation of pre-existing pathological conditions, including addiction. One of the factors that can influence the precise synchronization of the circadian system is the use and abuse of opioids. The interrelationship between the circadian and opioid systems is poorly studied. To this end, the present study investigated the effect of morphine and methadone on the rat circadian system in adulthood and during development. The aim of this dissertation was to observe the effect of acute morphine administration on the expression of clock genes in the suprachiasmatic nuclei (SCN) of adult rats, and to investigate the effect of long-term morphine or methadone administration and withdrawal on the expression of clock genes in the SCN and on the activity of the enzyme AA-NAT in the pineal gland of adult rats. Proper development of the circadian clock contributes significantly to the maintenance of health in adulthood and ensures good adaptability of the organism to changes in the external environment. No study to date has focused on examining the effects of opioid administration during...
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