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The role of Arachidonic acid metabolites in cardiovascular system and signaling of heart failure
Liptáková, Andrea ; Žurmanová, Jitka (advisor) ; Holzerová, Kristýna (referee)
Arachidonic acid (AA) is polyunsaturated acid that plays an important role in regulation of physiology, bioenergetic and signalling cascades in the heart. AA released by phospholipase A2-catalysed hydrolysis of membrane phospholipids serves as substrate for cyclooxygenase, lipooxygenase and cytochrome P450 epoxygenase to produce a wide spectrum of lipid second messengers, eicosanoids. These very biologically potent molecules regulate a number of cellular processes in the cardiovascular system and changes in their composition and concentration significantly contribute to heart failure. The aim of this thesis was to summarize current knowledge about the role of AA in failing heart. Keywords : Heart, Arachidonic Acid, Heart Failure, Eicosanoids, Cardiovascular System
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Organization of myofibrillar PCr/CK system in skeletal muscle
Žurmanová, Jitka ; Mejsnar, Jiří (advisor) ; Nováková, Olga (referee) ; Neckář, Jan (referee)
5. SUMMARYOFRESULTES Áll resultshavebeenpublishedor acceptedin joumalswith IF. Ite list of publicďionis enclosedin thechaoter6. 1) Lcvcls of cneigr-rclated metabolitcsin intect and isolated pcrfuscd-supcrfused rrt ske|ctálmusc|e*(ŠteÍleta],1991) AdenosineS'.triphosphate(ATP), phosphocreatine(PCr), creatirre(Cr), ínorganicphosphate (Pi),lactate(LAC), pyruvate(PYR) andglycogenasglucose(GLU) weredeterminedandfree adenosineS'-diphosptrate(ADP) was calculatedtom ATP:creatinephosphokinase(CPK) reactionin the gracilis muscleof cold.acc|imatedrďs in vivo. and in completelyisoIated mrsc|esundermediumperfusionandzuperfusionínvito, rsing thefreeze-clampingmetlrcd. Themeanin vivo leve|s(pmoVgw.w.)were:ATP 4.8'PCr 12.0.Cr 7,8'Pi ló.l' LAc l.6' PYR 0.09,GLU 22.9,ADP 0,62x t0-3.[solationof the muscle(about11min of anox'a fo|lowedby perfision irrthe air with a highpo2 Inedium)decreasedmacroergicphosphďe levels(ATP 3.0.PCr 8.3).Inisolatedmusclesperfusedwitha highpO2medium(99kPaOz, perflrion rate70 pl/mitt)andsimultaneouslysupeďusedwitha low po2medium(ó.2kPao2' 2.3mVmin)at28oC in vitrothelevelsof metaboliteswere(pmoUgw.w.):ATP 3.1,PCr 8.5, Cr 5.ó.Pi 9'2, |Ac 2.|' PYR 0.l9. GLU 6.6'ADP 0.44x l0(.]).Themeansteadyoxygen upuke of the íso|atedmusclewas 97 nmol 02 x min.l x g.l w.w. Ttrus.thelevelsof macroergicphosphatesand their...
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The function of p53 protein in mitochondria
Magdálková, Kateřina ; Kalous, Martin (advisor) ; Žurmanová, Jitka (referee)
Protein p53 is known as a tumor suppressor. In nucleus, p53 regulates the expression of its target genes, which are involved in cell cycle control, DNA repair and cell death. Protein p53 also has transcription-independent activities outside the nucleus. Under physiological conditions, certain amount of this protein can be found in mitochondria, where it is involved in mitochondrial genome integrity maintaining. Under stress conditions, p53 protein rapidly translocates to outer mitochondrial membrane or mitochondrial matrix, and takes a part in apoptotic or necrotic signaling pathway. Keywords: p53, mitochondria, mtDNA, apoptosis
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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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Pharmacological and metabolic influence on liver mitochondrial functions
Sobotka, Ondřej ; Červinková, Zuzana (advisor) ; Kuncová, Jitka (referee) ; Žurmanová, Jitka (referee)
Liver mitochondria play a crucial role in intermediary metabolism and main metabolic pathways. We evaluated the pharmacological effect on liver mitochondria in vitro using two novel anticancer drugs: 3-bromopyruvate and α-tocopheryl succinate. Metabolic influence on liver mitochondria was performed in vivo by high fat and high cholesterol diet. Toxicity of both drugs was evaluated in cell cultures of hepatocytes isolated from rat and mouse liver. The effect of anticancer drugs on liver mitochondrial functions in vitro was studied on suspensions of isolated liver mitochondria, tissue homogenate and permeabilized hepatocytes. Mitochondrial respiration was measured using high-resolution respirometry. 3-bromopyruvate caused morphological and functional damage of primary rat and mouse hepatocytes in cell cultures; this toxic effect was accompanied by an increase of reactive oxygen species production and mitochondrial dysfunction. 3-bromopyruvate decreased the oxygen consumption of mitochondria energized by substrates for complex I and complex II. α-Tocopheryl succinate caused a decrease of succinate-dependent respiration in all experimental models both in coupled and in uncoupled states. The most pronounced effect of α-tocopheryl succinate was apparent in isolated mitochondria and the least pronounced...
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Energy Metabolism in Obesity: Metabolic Flexibility and Dietary Fat
Bardová, Kristina ; Kopecký, Jan (advisor) ; Drahota, Zdeněk (referee) ; Žurmanová, Jitka (referee)
Abstract Adipose tissue is an important homeostatic tissue within the body. It not only buffers FA availability in the organism, but also releases important autocrine, paracrine or endocrine factors influencing energy metabolism. The biology of adipose tissue is closely related and underlies whole-body metabolic consequences of obesity, such as type II. diabetes. Obesity and type II. diabetes causes and maybe are caused by metabolic inflexibility, the inability of organism to adapt fuel oxidation to fuel availability. The intersection of adipose tissue biology, obesity and its metabolic consequences and theory of metabolic flexibility is discussed in this PhD. thesis. Five articles dealing with above mentioned topics are included. The general goal of this study was to compare several approaches for metabolic flexibility assessment with respect to overall energy homeostasis. The specific goals, delineated by included articles, were (i) to evaluate the influence of n-3 long chain fatty acids (n-3 LC-PUFA), rosiglitazone, and their combination, on metabolic flexibility at a whole-body and cellular level; (ii) to evaluate impact of high-fat feeding on metabolic flexibility of male and female mice; (iii) to evaluate the impact of chenodeoxycholic acid (CDCA)...
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Mitochondrial respiration at cold acclimated rats. Comparison of tissues.
Flégrová, Eliška ; Žurmanová, Jitka (advisor) ; Nováková, Olga (referee)
Acclimation to cold or hardening is known for many decades through its beneficial effects on human health. In contrast, sudden exposure to cold, cold shock, is a great risk of cerebral and cardiac injury, especially in the elderly. There is very little published data on the cellular and molecular mechanisms induced by cold adaptation in heart and brain. The aim of this work was to describe and compare different properties heart, liver, brain and brown adipose tissue mitochondria of rats housed at 25 ± 1 řC and at mild cold (9 ± 1 řC, 5 weeks). The high-resolution oxygraphy, spectrophotometry and Western blotting analyses were used. We found differences in the respiratory control between the heart and liver. Cold acclimation decreased activity of the Krebs cycle enzymes. Fatty acid contribution to the respiration reached the maximum in brown fat and the minimum in the hippocampus. However, further study is necessary.
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