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The role of RhoA/Rho kinase signalling pathway in the regulation of blood pressure in normotensive and hypertensive rats
Brunová, Aneta ; Zicha, Josef (advisor) ; Wasková, Petra (referee)
Evidence is accumulating that point to a major role of Rho kinase in arterial pathophysiology. Rho kinase is a key enzyme in calcium sensitization in vascular smooth muscle cells. Calcium sensitization is characterized as an increase in vascular contractility in the conditions of constant cytosolic calcium level. Inhibitors of Rho-kinase exert beneficial effects on the cardiovascular system, mainly by lowering vascular contractility. This thesis summarizes the current progress in understanding of the signaling pathways involved in the control of peripheral resistance of spontaneously hypertensive rats (SHR). It is evident that enhanced sympathetic activity and abnormal regulation of ion channel activity collectively contribute to high blood pressure maintenance in SHR.
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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
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 RhoA/Rho kinase signalling pathway in the regulation of blood pressure in normotensive and hypertensive rats
Brunová, Aneta ; Zicha, Josef (advisor) ; Wasková, Petra (referee)
Evidence is accumulating that point to a major role of Rho kinase in arterial pathophysiology. Rho kinase is a key enzyme in calcium sensitization in vascular smooth muscle cells. Calcium sensitization is characterized as an increase in vascular contractility in the conditions of constant cytosolic calcium level. Inhibitors of Rho-kinase exert beneficial effects on the cardiovascular system, mainly by lowering vascular contractility. This thesis summarizes the current progress in understanding of the signaling pathways involved in the control of peripheral resistance of spontaneously hypertensive rats (SHR). It is evident that enhanced sympathetic activity and abnormal regulation of ion channel activity collectively contribute to high blood pressure maintenance in SHR.
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The role of FAT/CD36 trasporter in the pathophysiology of heart
Kovalčíková, Jana ; Nováková, Olga (advisor) ; Wasková, Petra (referee)
1. Abstract FAT/CD36 is an 88 kDa glycoprotein that plays a key role in the transport of long- chain fatty acids (LCFA) through the plasma membrane in heart, skeletal muscle and adipose tissue. It participates in the fatty acids (FA) transport together with other membrane proteins, which are fatty acid transport proteins (FATP1-6), the plasma membrane fatty acid binding protein (FABPpm) and cytosolic fatty acid binding protein (FABPc). In cardiac tissue are, except FAT/CD36, only represented FABPpm, FATP1 and 6 and heart type of FABPc, referred to as H-FABPc. In addition to this protein mediated FA transport, FA are already known to be transported by passive diffusion. The cell expression of FAT/CD36 is regulated by nuclear peroxisome proliferators- activated receptor (PPAR), in the heart primarily by PPAR- . Inactive FAT/CD36 is found in intracellular depots, while active FAT/CD36 is present on the plasma membrane in lipid rafts. The two most known pathways regulating the FAT/CD36 translocation from the depots to the membrane are the insulin signalling pathway, which involves the activation of the enzyme phosphatidyl-inositol-3-kinase (PI3K) and cardiac contraction activated cascade, which activates adenosinmonophosphate kinase (AMP kinase). Furthermore, FAT/CD36 can as well be regulated by ubiquitination...
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