National Repository of Grey Literature 35 records found  1 - 10nextend  jump to record: Search took 0.00 seconds. 
Proteomic analysis of myocardial integral membrane proteins
Oliva, Tomáš ; Petrák, Jiří (advisor) ; Pompach, Petr (referee)
Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality in Europe. Over 4 million people die from CVDs annually and another 11 million people develops CVDs every year. These numbers show that there is a need for better diagnostic, prognostic and predictive biomarkers and, more importantly, a need for new and more efficient drugs. Integral membrane proteins (IMPs) are ideal candidates for new drug targets. However, a study of IMPs represents a major challenge in current proteomics. This challenge is associated with the low abundance of IMPs, their low solubility in aqueous solvents and the absence of trypsin cleavage sites in their transmembrane segments. To overcome these issues, methods that selectively target either N-glycosylated extra-membrane segments (CSC, SPEG, N-glyco-FASP) or transmembrane segments (hpTC) were developed. In this thesis we employed a combination of two N-glyco-capture methods (SPEG and N-glyco-FASP) performed on two different samples (membrane-enriched fraction and total tissue lysate) with analysis of membrane-embedded IMP segments by hpTC and with standard non-targeted "detergent+trypsin" approach to analyze rat myocardial membrane proteome. We also performed an evaluation of employed methods for preparation of membrane fraction by western blot...
Role of protein kinase C isoforms in cardioprotective mechanism of chronic hypoxia
Hlaváčková, Markéta
Cardiovascular diseases, particularly acute myocardial infarction, are one of the leading causes of death in developed countries. It is well known that adaptation to chronic intermittent hypobaric hypoxia (IHH) confers long-lasting cardiac protection against acute ischemia/reperfusion injury. Protein kinase C (PKC) appears to play a role in its cardioprotective mechanism since the administration of general PKC inhibitor completely abolished the improvement of ischemic tolerance in IHH hearts. However, the involvement of individual PKC isoforms remains unclear. Therefore, the primary aim of this study was to investigate the potential involvement of PKCδ and PKCε, the most prevalent PKC isoforms in rat heart, in the mechanism of IHH-induced cardioprotection. We showed that IHH up- regulated PKC protein in left ventricle, enhanced its phosphorylation on Ser643 and increased its co-localization with markers of mitochondrial and sarcolemmal membranes. PKCδ subcellular redistribution induced by IHH as well as the infarct size-limiting effect of IHH was reversed by acute treatment with PKCδ inhibitor rottlerin. These data support the view that PKCδ plays a significant role in IHH-induced cardioprotection. On the other hand, adaptation to IHH decreased the PKC total protein level without affecting its...
The effect of opioids on the redox state of rat myocardium
Jandová, Gabriela ; Novotný, Jiří (advisor) ; Roubalová, Lenka (referee)
The aim of this work was to study the expression of proteins involved in reactions in which harmful free radicals are degraded in an organism. was observed difference between the expression of selected myocardial proteins in non-influenced animals, animals who were treated with low dosage of morphine (0.1 mg/kg/day or 1 mg/kg/day), and animals administered high dosage of morphine (10 mg/kg/day). Low dosages were administered for 28 days and high dosage for 10 days. In addition, the effect of abstinence lasting one week was assessed after cessation of morphine administration (1 mg/kg/day). Morphine at low dosage (0.1 mg/kg/day) increased levels of glutathion peroxidase-1/2, which may be considered as one of the possible consequences of the ongoing oxidative stress. There were no significant differences in glutathion peroxidase-6 expression. Next aim of this work was to study the expression of antioxidant enzymes. These experiments were carried out on myocardial preparations from the animals treated with a constant dosage of morphine (10 mg/kg/day) for 10 days. Samples from these animals were used for measuring the total antioxidant capacity of the left and right ventricles. These samples were also used for determination of concentration of the oxidative stress marker 8-isoprostane. We also aimed to...
Gene expression of enzymes involved in the regulation of apoptosis in rat moycardium - effect of chronic and acute hypoxia
Blahová, Tereza ; Žurmanová, Jitka (advisor) ; Kalous, Martin (referee)
Adaptation to chronic hypoxia provides myocardial protection against ischemia - reperfusion injury (IR). Cardioprotective effect of adaptation depends on the degree and duration of hypoxic exposure and daily regime of adaptation. Certain protective regimes of adaptations to hypoxia have been reported to activate proapoptotic signaling pathways and bioactive sphingolipids were recently shown to play important role in the regulation of apoptosis in the heart. We aimed to determine the mRNA level of selected genes related to apoptotic pathways and to sphingolipid metabolism in two models of hypoxic adaptation, continous normobaric hypoxia (CNH 10% O2) with different exposures (4h, 48h, 120h, 21days) and intermitent hypobaric hypoxia (IHH 7000 m, 8h/day). Both ventricles, LV and RV, were analysed after adaptation to CNH and only LV was analysed after IHH adaptation. Our results show that both types of adaptation increased mRNA of proapoptotic genes, CNH mainly in RV and IHH in LV. Furthermore, increased expressions of proapoptotic genes were accompanied by the increase of expression of enzymes producing predominantly protective kinds of sphingolipids. The exact role of apoptosis and sphingolipid signaling molecules in endogenous myocardial protection requires further research. Key words: Apoptosis,...
Effect of chronic hypoxia on antioxidative capacity of rat myocardium.
Závišková, Kristýna ; Nováková, Olga (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia activates endogenous signaling cascades, which lead to cardiac protection against acute ischemia/reperfusion (I/R) injury. The molecular mechanism of this phenomenon has not been fully clarified yet. However, it was proved that reactive oxygen species (ROS) take part in cardioprotective signaling pathway inducted by chronic hypoxia. The high level of ROS must be precisely regulated by antioxidative system of a cell. The aim of diploma thesis was to examine the effect of intermittent hypobaric hypoxia (IHH, 7 000 m) on relative amount of antioxidative enzymes (peroxiredoxin 6 - PRX6, thioredoxin 1 and 2 - TRX1 and TRX2, thioredoxin reductase 1 - TRXR1) and also enzymes of iron metabolism (heme oxygenase 1 and 2 - HO1 and HO2, aconitase 1 and 2 - ACO1 and ACO2), which participate in regulation of cell redox state. Moreover, we studied the effect of adaptation to IHH and an antioxidant tempol on relative amount of calcium-independent phospholipase A2 (iPLA2). iPLA2 can remove peroxidized fatty acids from membrane phospholipids. On the other hand, iPLA2 can damage cell in I/R conditions. All enzymes were studied in homogenates from normoxic and IHH adapted rat left ventricular myocardium by Western blot. Adaptation to IHH caused a decrease of PRX6 and on the opposite an increase of...
Functional morphology of myocardium
Vebr, Pavel ; Žurmanová, Jitka (advisor) ; Míčová, Petra (referee)
The thesis is a literary review summarizing current knowledge about the ultrastructure of myocardium in the overall context of the development and anatomy of the heart. The first part of the study is a summary of heart anatomy and its embryonic development, with emphasis on the morphology of cardiomyocytes. The state of inner cytoarchitecture of myocardial cells and the quality of inter-cellular connection reflects the functionality of the heart. Location and condition of cell compartments reflect the overall condition of the cell. The following part is devoted to the basic microscopic analysis methods suitable for research ultrastructure of cardiac cells. The outcome of this work is a comprehensive overview of the organization of remarkable morphological formations in cardiomyocyte, possible changes in ultrastructure in context of physiological conditions and comparison of microscopic methods with regard to their use in research of cardiomyocytes ultrastructure. Powered by TCPDF (www.tcpdf.org)
Cardiac ischemic tolerance of hypertensive rats
Jelínek, Jan ; Neckář, Jan (advisor) ; Kašparová, Dita (referee)
The aim of this thesis is to summarize current knowledge about the influence of the ischemic- reperfusion injury at the myocard of hypertensive subjects. First part of this thesis is focused on the description of ischemia, reperfusion and changes in the myocardial metabolism during these processes. These changes in the myocardial metabolism are for example necrosis or apoptosis of the myocardial cells. The second part describes the currently known cardioprotective phenomena. This part also compares their effects. The signalization of preconditioning, the second window of preconditioning and the postconditioning are described here in more details. Third part is focused on the description of the risk factors connected to the ICHS and hypertension. It describes also classes of hypertension, clinical and experimental methods of hypertension treatment, description of the laboratory breeds of hypertensive rats. In the last part of this thesis I describe the influence of hypertension on the I-R injury in current laboratory studies. In the most studies spontaneously hypertensive rats (SHR) were used. As a normotensive controls Wistar-Kyoto rats were mostly used. For some other experiments transgenic genetic rats (TGR) were used. Powered by TCPDF (www.tcpdf.org)
Effect of erythropoietin on myocardial ischemic tolerance
Jindrová, Helena ; Kolář, František (advisor) ; Žurmanová, Jitka (referee)
Adaptation to chronic hypoxia increases myocardial resistance to acute ischemia/reperfusion (I/R) injury, similarly to application of exogenous erythropoietin (EPO). Nevertheless, it is not known if EPO induced by chronic hypoxia plays a role in its cardioprotective mechanism. The aim of this study was to find out if protective effect of exogenous EPO adds up to protection offered by chronic hypoxia. Adult male mice (ICR) were adapted to intermittent hypobaric hypoxia 8 hours per day, 5 days per week for 5 weeks. The degree of hypoxia corresponded to 7000 metres. Control animals were housed for the same time in normoxic environment. Resistance to I/R injury was assessed according to size of myocardial infarction induced by 45-min global ischemia and 1-h reperfusion of the heart in vitro. Animals were treated 24 h before the experiment with 200 or 5000 U/kg EPO. Treatment with 200 U/kg EPO was sufficient to significantly limit infarct size in normoxic animals (33,56 ± 2,93 % vs. 25,71 ± 2,29 %). Hypoxic adaptation decreased infarct area to 23,49 ± 2,30%, but additive effect of EPO in hypoxic group was not detected. The results indicate that exogenous EPO employs the same cardioprotective mechanisms as adaptation to chronic intermittent hypoxia. Preliminary results indicate that repeated application of EPO...
The effect of morphine on expression and distribution of the alpha and beta subunits of trimeric G-proteins in the rat myocardium
Bartoňová, Iveta ; Novotný, Jiří (advisor) ; Roubalová, Lenka (referee)
Morphine is a clinically very important drug from the opioid group that is used for treatment of severe pain because of its strong analgetic effect. Opioid receptors mediating the morphine effect interact with the Gi/o class of trimeric G-proteins. Opioid receptors also occur in heart tissue and morphine can thus potentially exercise its effect on the function of this organ. The major aim of this project was to pursue consequences of long-term treatment with morphine on expression and distribution of selected heterotrimeric G-protein subunits in the rat heart. Potential cardioprotective effects of this drug have also been studied. Laboratory rats of the Wistar strain were treated with morphine (1 mg/kg/day or 10 mg/kg/day) for 10 or 28 days. The control group was treated with saline solution. Prolonged treatment with morphine did not cause any effects on Gs, Gi, Gz, Gq/11, G subunits, but the expression of Go rather decreased. The results of subsequent experiments showed that prolonged administration of high doses of morphine may reduce the area affected by infarction and reduced the frequency of ventricle arrhythmias depending on dose and duration of morphine administration. Key words: morphine, myocardium, opioid receptor, G-protein subunits, infarction.

National Repository of Grey Literature : 35 records found   1 - 10nextend  jump to record:
Interested in being notified about new results for this query?
Subscribe to the RSS feed.