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The role of PCr/CK shuttle in adult rat myocardium under normoxic hypoxic conditions
Honcová, Lada ; Žurmanová, Jitka (advisor) ; Novotný, Jiří (referee)
The creatine kinase (CK) is an important enzyme of cell energy metabolism in excitable tissue. It occurs in four isoforms. Two cytosolic isoforms are functional in mono and hetero dimers and two mitochondrial isoforms reach tetramer and octamer forms. Its primary function is the regeneration of ATP close to ATPases and phosphocreatine pool from creatine and ATP, which gives its posphate in places of acute requirements of high energy demand. Dysfunction of CK is connected with heart, muscle and neurological diseases and CK is often used as a clinical indicator. This work is focused to the role of CK in energy metabolism of hypoxia adapted myocardium. CK thaks to production of ADP in mitochondria decreases a membrane potential as well as production of reactive oxygen species (ROS). ROS cause most of damage during ischemic heart disease and infarct of myocardium. That`s why cardioprotective effects and CK itself during hypoxia are investigated.
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The role of mitochondrial creatine kinase and hexokinase in cardioprotective mechanisms induced by chronic hypoxia
Wasková, Petra
IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...
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Localization of cytosolic isoforms of creatine kinase and hexokinase in hypertrophied heart
Heleš, Mário ; Žurmanová, Jitka (advisor) ; Mrózková, Petra (referee)
Hypertrophy of the heart is tightly bound to the metabolic adaptations and a cellular remodeling. An important and dynamic system contributing to the maintenance of energy homeostasis is the creatine kinase system (CK). The microcompartmentalization of CK isoforms maintains the flux of ATP between energy production and consumption sites and ensures the effectiveness of the CK system. Changes in expression and activity of CK isoforms during hypertrophy are already well described - to extend this knowledge, this thesis quantified changes in association of cytosolic CK isoforms and sarcomeres. Another essential system, maintaining homeostasis in overloaded heart is composed of the hexokinase (HK) isoforms, located also in cytosol and in mitochondrial compartment. HK1 is associated with mitochondria under physiological conditions, maintaining mitochondrial membrane potential, while HK2 is located mainly in the cytosol. Under stress conditions translocation of HK2 into mitochondrial membrane occurs, which increases the direct supply of ADP to complex V of the respiratory chain and decreases the probability of apoptosis activation. We analyzed association of individual HK isoforms with mitochondria within the second aim of this thesis. Third aim of the thesis was to characterize changes in the CK and M...
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The role of mitochondrial creatine kinase and hexokinase in cardioprotective mechanisms induced by chronic hypoxia
Wasková, Petra
IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...
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The role of mitochondrial creatine kinase and hexokinase in cardioprotective mechanisms induced by chronic hypoxia
Wasková, Petra ; Žurmanová, Jitka (advisor) ; Drahota, Zdeněk (referee) ; Nováková, Olga (referee)
IN ENGLISH The ischemia-reperfusion (I/R) injury, which is a consequence of myocardial infarction, represents a major cause of death worldwide. One of the most effective cardioprotective interventions increasing the resistance of hearts to the I/R injury is the adaptation to a chronic hypoxia (CH). However, the molecular mechanisms of CH are still not well understood. The most important factors responsible for the I/R injury are reactive oxygen species (ROS) produced by complexes I and III within the mitochondrial electron transport chain. Potential candidates maintaining ROS at a low level are mitochondrial creatine kinase (mtCK) and two hexokinase isoforms (HK1 and HK2). These enzymes highly support the mitochondrial oxidative phosphorylation by increasing the availability of ADP for complex V of the respiratory chain. In addition, the HK binding to mitochondria inhibits binding of the pro- apoptotic protein BAX, thereby protecting cardiac cells against apoptosis. Besides the mitochondrial CK isoform, there are two cytosolic CK (CKM and CKB) present in cardiomyocytes that help to maintain energy homeostasis. Based on the known anatomical and physiological differences between the left (LV) and the right (RV) ventricles, the first study focused on the comparing ventricles in terms of the energy...
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The role of PCr/CK shuttle in adult rat myocardium under normoxic hypoxic conditions
Honcová, Lada ; Žurmanová, Jitka (advisor) ; Novotný, Jiří (referee)
The creatine kinase (CK) is an important enzyme of cell energy metabolism in excitable tissue. It occurs in four isoforms. Two cytosolic isoforms are functional in mono and hetero dimers and two mitochondrial isoforms reach tetramer and octamer forms. Its primary function is the regeneration of ATP close to ATPases and phosphocreatine pool from creatine and ATP, which gives its posphate in places of acute requirements of high energy demand. Dysfunction of CK is connected with heart, muscle and neurological diseases and CK is often used as a clinical indicator. This work is focused to the role of CK in energy metabolism of hypoxia adapted myocardium. CK thaks to production of ADP in mitochondria decreases a membrane potential as well as production of reactive oxygen species (ROS). ROS cause most of damage during ischemic heart disease and infarct of myocardium. That`s why cardioprotective effects and CK itself during hypoxia are investigated.
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Analysis of selected gene transcripts in the rat myocardium adaptated to chronic hypoxia
Kašparová, Dita ; Žurmanová, Jitka (advisor) ; Nováková, Olga (referee)
Dita Kašparová Chronická hypoxie a exprese genů 4 Abstract Adaptation to chronic hypoxia (CH) is characterized by a variety of functional changes in order to maintain metabolic and energy homeostasis. It has been known for many years that both humans and animals indigenous or adapted to high-altitude hypoxia are more tolerant to an acute ischemic injury of the heart. Cardioprotective mechanisms activated by adaptive responses to chronic hypoxia can be the result of altered transcriptional regulations in left ventricles. Here we report results from the gene expression profiling of adaptive responses in three models of chronically hypoxic heart. Adult male Wistar rats were exposed for 21 days to either continuous normobaric hypoxia (CCH; 10% O2) or CCH interrupted daily by 1-hour reoxygenation (RCH) or CCH interrupted daily by 16-hour (CIH). Cardiprotective effect of CCH adaptation is abolished by brief daily reoxygenation, RCH adaptation. In the present study, we aimed to determine myocardial mRNA expression of 19 candidate genes divided into three important groups: i) Hypoxia inducible factor (HIF1α) and its prolyl and asparaginyl hyroxylases (PHDs and FIH respectively, ii) Creatine kinase (CK) isoenzymes which play important role in energy homeostases of heart and iii) the group of main enzymatic...
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