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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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Cold perception and cold receptors
Kužílková, Johana Abigail ; Žurmanová, Jitka (advisor) ; Ptáková, Alexandra (referee)
Cold perception is a crucial sensory phenomenon for the survival of most organisms. It facilitates the selection of appropriate thermoregulatory responses necessary for maintaining organismal integrity and aids in spatial orientation. However, the mechanisms underlying cold perception remain incompletely understood. Central to this process are cold receptors, proteins capable of depolarizing cells and eliciting action potentials in response to cold stimuli. This study aims to review and understand the current literature on two key aspects related to cold perception. Firstly, it seeks to elucidate how contemporary knowledge explains an organism's ability to discern a wide range of cold temperatures. Secondly, it endeavours to explore the identified or hypothesized cold receptors and the extent of our knowledge regarding their functional role in the perception of cold. Key words: Cold perception, cold activated receptors, TRPM8, TRPA1, TRPC5
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Functions of Neuregulin 4
Majerčáková, Eva ; Žurmanová, Jitka (advisor) ; Haasová, Eliška (referee)
This work focuses on reviewing the function of Neuregulin 4 (Nrg4) and its receptor ErbB4 in various biological processes and disease states, including inflammation, cancer, metabolic diseases, and liver diseases. In metabolic diseases such as diabetes, Nrg4 may affect glucose metabolism and lipid homeostasis, but the exact mechanism of action is not yet well understood. Nrg4 and its receptor ErbB4 appear to be key factors in regulating inflammation and promoting cell survival. Moreover, in liver diseases, such as nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, Nrg4 and ErbB4 seems to play a protective role. Overall, these findings highlight complex roles of Nrg4 and ErbB4 in a multitude of biological processes and disease states. Further research is needed to fully understand these relationships and their potential as diagnostic or therapeutic targets.
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Mechanism of cardioprotection elicited by cold acclimation
Csomová, Martina ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Myocardial infarction is the most common cause of death and disability worldwide. The term myocardial infarction refers to the death of cardiac cells, cardiomyocytes, caused by ischaemia resulting from a perfusion imbalance between the supply and demand for oxygen and nutrients. Recently, cold acclimatization has been found to reduce infarct size after ischemia/reperfusion (I/R) injury, but the mechanism is not fully clarified. Cold acclimatization elicits a thermoregulatory response by activating nontalamic thymogenesis associated with brown adipose tissue (BAT) activation. Cold-stimulated adrenergic signaling increases the expression of mitochondrial uncoupling protein 1 (UCP1), a key factor for heat production. Activated BAT increases metabolic turnover and thus likely contributes to the protection of the heart from myocardial infarction. In this work, I simulate I/R injury by establishing a hypoxic- reoxygenation (H/R) protocol in isolated adult cardiomyocytes. The aim of this work was to introduce different approaches to assess the viability of isolated cardiomyocytes and compare their utility, to investigate the effect of different cold adaptations on cardiomyocyte viability during the H/R protocol using the Cytation 5 multidetector, and subsequently to determine the effect of inhibitors of...
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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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Energetic metabolism of heart during acut and chronic hypoxia
Kolář, David ; Žurmanová, Jitka (advisor) ; Sotáková, Dita (referee)
The heart is a highly oxidative tissue, which far exceeds the oxygen consumption of neurons. The centre of ATP production is therefore in oxidative phosphorylation, which is contributed to by different substrates (glucose, fatty acids and lactate) depending on metabolic conditions. A high proportion of mitochondria in heart tissue carries an increased risk of reactive oxygen species development in the possible disruption of mitochondrial metabolism. Oxygen radicals are generated primarily at complex I and III of the respiratory chain of mitochondria. They may perform a signalling role allowing the heart adaptation to hypoxia, but the high concentration leads to irreversible damage /of cellular structures. This thesis considers the energy metabolism of the heart under normoxic, hypoxic and ischemic conditions, with emphasis on the glucose and fatty acids uptake, and the control of oxidative phosphorylation.
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Effect of morphine on the resistance of the heart to ischemia
Mošovská, Linda ; Neckář, Jan (advisor) ; Žurmanová, Jitka (referee)
2. Abstract Opioids are considered as dangerous and addictive substances, mainly due to synthetic opioids such as heroin. It was discovered, that these substances can play an important role in myocardial ischemia because they can limit the damage of the heart tissue that occurs during a heart attack. Since that heart attack is the most common cardiovascular disease, the protective effect is significant. Cardioprotective effect is mainly mediated through δ opioid receptors, but the few studies have shown cardioprotective effect mediated through κ opioid receptors. The protective effect occurs by activation of opioid receptors by their agonists (eg. morphine or TAN-67), either before ischemia (opioid preconditioning) or before reperfusion (opioid postconditioning). The signaling pathway of cardioprotection include mitochondrial KATP channel, Gi/o proteins, protein kinase C, tyrosine kinases and reactive oxygen species.
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