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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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Target genes and regulation of hypoxia inducible factors HIF1a a HIF2a
Blahová, Tereza ; Žurmanová, Jitka (advisor) ; Alánová, Petra (referee)
Oxygen supply is necessary for today's form of life on Earth. Molecular oxygen is a terminal electron acceptor in mitochondrial respiratory chain and enables the efficient production of ATP by oxidative phosphorylation. The lack of availability of oxygen decreases energy production and can endanger the processes maintaining homeostasis. Therefore the compensatory mechanisms were developed by which cells respond to hypoxia. The master regulator of cellular responses is the hypoxia inducible transcription factor, HIF. In general HIF-1 isoform supports glucose availability and glycolysis; also attenuates energy-consuming processes and thus reduces energy loss. HIF-2 isoform stimulates antioxidant mechanisms to reduce the amount of reactive oxygen species which could cause cellular damage. At the same time, both of isoforms contribute to increasing the supply of oxygen by activating erythropoiesis and angiogenesis in the affected area. HIFs provide these changes either directly, by using their target genes, or by interactions with other transcription factors and signaling pathways.
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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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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra ; Neckář, Jan (advisor) ; Nováková, Olga (referee) ; Vaněčková, Ivana (referee)
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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Evaluation of opioid and TLR-4 receptors in the mechanism of opioid effects on heart muscle cells
Biriczová, Lilla ; Novotný, Jiří (advisor) ; Alánová, Petra (referee)
It has been reported that opioid receptor activation mimics ischemic preconditioning, which may protect the heart from the development of infarction. Toll-like receptor 4 (TLR-4) during infarction stimulates cytokine production leading to inflammation and injury of the heart tissue. Our aim was to study the effect of morphine in vitro on the viability and oxidative state of H9c2 cells (rat cardiomyoblasts) and the role of TLR-4 during oxidative stress. Our experiments showed that pretreatment with morphine before tert-butylhydroperoxide (t-BHP)-, 2,2'-bipyridyl (BP)- and lipopolysaccharide (LPS)-induced oxidative stess had protective effect on the viability of H9c2 cells and markedly reduced the production of reactive oxygen species (ROS). The protective effect of morphine was diminished after naloxone treatment, which confirms the role of opioid receptors in preconditioning. TLR-4 inhibition by TAK-242 pretreatment and silencing TLR-4 by RNA interference resulted in a partial increase in cell viability but significant attenuation of ROS production after t-BHP and BP treatment. The action of LPS was reduced in response to TLR-4 silencing. Interestingly, naloxone pretreatment and suppression of TLR-4 markedly alleviated oxidative stress and resulted in a significant improvement of cell viability. We...
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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra ; Neckář, Jan (advisor) ; Nováková, Olga (referee) ; Vaněčková, Ivana (referee)
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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Myocardial tolerance to ischemia/reperfusion injury - possible protective mechanisms
Alánová, Petra
Ischemic heart disease is the leading cause of death and disability worldwide. The effects of ischemic heart disease are usually attributable to the detrimental effects of acute myocardial ischemia/reperfusion (I/R) injury. The aim of the thesis was to contribute to current effort to clarify the basis of mechanisms that could save the heart from I/R injury. The whole thesis is based on four studies; while the first three are published, the fourth one has been under revision. In the first study, we proved the involvement of nitric oxide (NO) in the cardioprotective mechanism of chronic hypoxia (CH). We described that exogenously increased availability of NO as well as inhibition of phosphodiesterase type 5 led to increased myocardial tolerance of normoxic and chronically hypoxic rats. The effects of both interventions were not additive, suggesting that NO is included in cardioprotective signaling of CH. Second study continued in investigating molecular mechanisms underlying cardioprotection induced by CH. We showed that infarct size-limiting effect of adaptation to CH was accompanied by increased myocardial concentration of tumor-necrosis factor alpha (TNF-α) and TNF-α receptor R2. In the third study, we examined the effect of dexrazoxane (DEX), the only clinically approved drug against...
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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 nitric oxide in the patophysiology of neurodegenerative diseases
Matušková, Hana ; Otáhal, Jakub (advisor) ; Alánová, Petra (referee)
The bachelor thesis deals with the importance of nitric oxide in the development of neurodegenerative diseases. Nitric oxide is a biological active gas which affects, among other things, many functions of the central nervous system. Its activity is dependent on the concentration in small amounts has a positive effect, while overproduction contributes significantly to the development of neurodegenerative diseases. In my work, I deal with the negative influence of nitric oxide in the development of epileptic seizures, Parkinson's disease, Alzheimer's disease and Huntington's disease. In conclusion, I mentioned the possibility of determining the amount of nitric oxide concentration. Keywords Nitric oxide, ROS, RNS, neurodegenerative diseases, epileptic seizures, Parkinson's disease, Alzheimer's disease, Huntington's disease
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