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The role of cold acclimation in ischemicko-reperfusion injury
Marvanová, Aneta ; Žurmanová, Jitka (advisor) ; Čížková, Dana (referee) ; Králová Lesná, Ivana (referee)
Cardiovascular disease, including ischemic heart disease, its acute form of myocardial infarction and subsequent heart failure, is still the most common cause of death in the world. For decades, scientists have been aiming to find clinically usable cardioprotective interventions that effectively prevented this disease or reduced the consequences of this disease and improved the quality of life of patients. It is known that a healthy lifestyle, which includes long-term hardening, contributes to heart protection. The beneficial effects of hardening on personality have been known for two hundred years, but no one before us has investigated the effect of a cold environment on the magnitude of ischemia-reperfusion (I/R) damage 10 years ago, we introduced a model of mild cold exposure (8 ± 1 řC) (MCE) which was protective on the size of the myocardial infarction and at the same time no negative side effects such as hypertension and myocardial hypertrophy were demonstrated. Our aim was to investigate the mechanism of cardioprotection induced by MCE. We asked the following questions: What is the metabolic profile of rats exposed to MCE? What is the effect of MCE on the magnitude of I/R damage in the short and long term? When does brown adipose tissue mature during MCE? Which signalling pathways are...
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The effect of chronic cold on Ca2+-ATPase (SERCA2) in rat heart
Šeovićová, Maja ; Horníková, Daniela (advisor) ; Nováková, Olga (referee)
Acute cold exposure is a significant stressor activating heat production by shivering after the prolonged exposure cellular oxidative stress increases. Chronic exposure to cold lasting at least 2 weeks leads to the development of cold acclimatization. The main thermogenic role is taken over by non-shivering thermogenesis taking place in brown adipose tissue, which significantly increases its weight due to cold. Cardiac hypertrophy, hypertension and impaired renal function are frequently observed pathologies of acclimatization at 4-5 řC. Our laboratory recently introduced a model of mild chronic cold acclimatization at 8 řC, during which no damage to the heart or kidneys occurs and has proven cardioprotective effect on reducing infarct size. Hence, the influence of this cold acclimatization model on the other cellular and molecular processes needs to be investigated. The cardioprotective effect of cold acclimatization includes changes in β-AR signaling, activation of anti-apoptotic pathways or augmentation of the antioxidant system. The aim of this thesis was to investigate the effect of cold acclimation and subsequent reacclimation on proteins regulating Ca2+ levels in the rat heart (SERCA2 and phospholamban) and on the stimulation of regulatory proteins β-arrestin 1/2 and protein kinase PDPK1. The...
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Jak rostliny vnímají chlad: omická analýza
Karšulinová, Daniela
Plants of temperate zones have developed a sophisticated mechanism that helps them cope with freezing conditions. This process is called cold acclimation. From an agronomical point of view, comprehending this process is necessary to ensure crop yield and quality. This thesis entitled: "Jak rostliny vnímají chlad: omická analýza" describes the molecular mechanism behind the cold acclimation process, specifically the role of light and selected photoreceptors in this process. In the experimental part of the thesis, a mutant line (UVR8 line12-monomer) of model organism Arabidopsis thaliana, which has a partially activated signaling of the UV-B, and the control line (Ws-4) were used. These lines were exposed to cold and UV-B radiation to further study the interaction of the cold signaling pathway and UV-B radiation signaling. LC-MS profiling identified more than 6000 proteins, of which 3472 significantly changed their abundance. Moreover, lipidome analysis was performed using TLC Proteomic analysis revealed an increased abundance of proteins involved in biosynthesis of jasmonic acid. Based on this, a validation experiment with exogenous application of methyl jasmonic acid was performed.
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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 batokines in cardioprotection elicited by mild cold acclimation
Zvolská, Veronika ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Myocardial infarction remains one of the most serious diseases of civilization worldwide. The aim of the research is therefore to search for new strategies to protect the heart from ischemia-reperfusion (I/R) damage and its consequences. New findings can be used in clinical practice and for the prevention and treatment of heart diseases. This work builds on a study from our laboratory that developed a model of mild cold acclimation (5 weeks, 8 řC) associated with a significant reduction in infarct size after rat myocardial I/R without side effects. However, further study is needed to elucidate the mechanism of the cardioprotective effect. The diploma thesis was focused on the potential influence of known batokines, fibroblast growth factor (FGF21) and interleukin 6 (IL-6). Furthermore, we aimed to introduce a method for isolating adult rat cardiomyocytes and a procedure for verifying the viability and resistance of myocardial cells under the load of hypoxia and oxidative stress at the workplace. Effective cardioprotection of the mild cold acclimation was confirmed in the work. Acute ablation of BAT before the ischemia-reperfusion protocol had no effect on infarct size. The cardiomyocyte isolation method was successfully introduced and the protective effect of acute cold (10 days, 8 řC) was...
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Role of antioxidant enzymes in cardioprotective regimens of cold acclimation
Špínová, Šárka ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
The effect of cold on the organism depends on the degree of cold and its duration. Cold acclimation induces a thermoregulatory response, shivering thermogenesis and subsequently the development of non-shivering thermogenesis associated with the activation of brown adipose tissue. Exposure to mild cold in the form of hardening possesses beneficial effects on the whole organism and recently the cardioprotective effects of mild cold acclimation has been described. Increased antioxidant capacity has been demonstrated in the mechanism of cardioprotection induced by hypoxia. The aim of this thesis was to find out whether the protective effect of mild cold acclimatization (8 ± 1 řC) is associated with a change in the capacity of the antioxidant system. To achieve this goal, the protein levels of the main antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, thioredoxin, thioredoxin reductase, aconitase, heme oxygenase) were determined during acclimation to mild cold, specifically in 1-3-10 days and subsequently after 5 weeks, and after a 2-week recovery. The results showed changes in most of the antioxidant proteins, however the effect on cold-elicited cardioprotection must be further verified. Key words: heart, cold acclimation, superoxide dismutase, catalase, glutathione...
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The role of PGC-1α during the development of a cardioprotective phenotype in a rat adapted to mild cold
Bajsová, Barbora ; Žurmanová, Jitka (advisor) ; Szeiffová Bačová, Barbara (referee)
Cold exposure elicits a thermoregulatory response in an organism. If the cold stimulus is sufficient, there is increased heat generation by shivering thermogenesis. Under prolonged action of the cold stimulus, shivering thermogenesis is replaced by non-shivering thermogenesis. Non-shivering thermogenesis in the rat takes place predominantly in brown adipose tissue (BAT), where the uncoupling protein 1 (UCP1) is activated in mitochondria under the control of adrenergic signaling. The activity of UCP1 is crucial for heat production. The coactivator PGC-1α plays an important role in mitochondrial biogenesis and in the energy metabolism of BAT and heart, and its function is associated with cardioprotection. Recently, the cardioprotective effects of mild cold adaptation at 8±1 řC were discovered in our laboratory, which reduced the size of ischemia-reperfusion injury without negative side effects. However, the molecular nature of the events induced by adaptation to mild cold is unknown neither in BAT nor in the heart itself. Therefore, the aims of the thesis were 1) to characterize the development of BAT at the level of expression of selected proteins and mitochondrial markers during acute cold exposure and chronic cold adaptation with subsequent recovery and 2) to determine the role of PGC-1α and...
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Ischemia-reperfusion injury in cold acclimated rats
Vebr, Pavel ; Žurmanová, Jitka (advisor) ; Alánová, Petra (referee)
The effect of cold acclimation on body of mammals has been studied for many decades by using relatively low temperatures for acclimation (6-10 řC). The results of these experiments have shown the important role of the adrenergic and thyroid system during acclimation and negative impact on renal system at the same time. In contrast, a recent study on winter swimmers suggests a possibility of positive influence of hardening on cardiovascular system. There is no available study investigating a relationship between cold adaptation and ischemia-reperfusion injury. The aim of this study was to establish a protocol of isolated rat heart and its fixation at our workplace. Furthermore, to find the impact of mild cold acclimation on the ischemia-reperfusion injury of rat. Methods of ex vivo heart perfusion and fixation were successfully established. The effect of 5 weeks long cold acclimation in 10 ± 2 řC on left ventricle ischemia-reperfusion injury was observed. Powered by TCPDF (www.tcpdf.org)
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The role of the adrenergic system in the process of cold acclimation
Dynybylová, Anna ; Novotný, Jiří (advisor) ; Brabcová, Iveta (referee)
The ability to keep constant body temperature is necessary for mammals. There are effective strategies developed during the evolution - shivering and nonshivering thermogenesis, which start during cold exposure. This thesis is focused on the nonshivering thermogenesis which occurs in brown adipose tissue and is controlled by norepinephrine released from the sympathetic nerves if the cold stress persists for a long time. The principle of the heat production is based on function of the uncoupling protein 1 which disrupts the proton gradient in mitochondria thereby releasing heat the waste product. Similar mechanism of energy dissipation is used not only during cold exposure but also after digestion of high fat diet, which may provide clues for potential therapeutic treatment of obesity and associated metabolic diseases. This study summarizes current knowledge about the role of adrenergic signalling in the process of cold acclimation. Key words: cold acclimation, nonshivering thermogenesis, brown adipose tissue, sympathetic nerve system, uncoupling protein 1 (UCP1), obesity
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