|
|
The entry of lead into the brain after experimental administration of lead acetate
Patková, Jana ; Vojtíšek, Maxmilián (advisor) ; Žurmanová, Jitka (referee)
Lead is a ubiquitous environmental toxin that induces a broad range of fysiological, biochemical and behavioral dysfunctions in man and in experimental animals. The present study is focused on the effect of lead on the central nervous system, which is considered to be most deleterious, especially alterations of cognitive and behavioral functions. New concepts in the neurotoxicology of lead include advances in understanding mechanisms of lead-induced damage to the nervous system, like induction of oxidative stress. In the experimental part the entry of lead into the brain of mature mice after long-term exposure to lead acetate (PbAc) and the influence of lead on cognitive function and motoric skills of exposed animals were observed. Cognitive function was tested in Morris water maze, motoric tests were performed on rotating cylinder and horizontal wire. Healthy and neurodefective Lurcher mutant mice were used. Further the influence of lead on the development of oxidative stress in the brain by fluorescent spectroscopy was studied. Lipofuscin-like pigments were used as indicators of oxidative stress. The prominent accumulation of lead in the brain of exposed animals as compared to controls was observed after the long-term exposure of mice to PbAc. No changes in motoric or cognitive functions in healthy or...
|
|
|
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.
|
|
|
The role of Akt kinase in cardioprotective mechanisms induced by chronic hypoxia
Grešíková, Milada ; Žurmanová, Jitka (advisor) ; Svatoňová, Anna (referee)
Cardiovascular diseases (CVDs) are the most widely spread diseases of modern civilization. Mechanisms involved in the protection of myocardial tissue are for that very reason in the focus of cardiovascular research. The adaptation to chronic hypoxia has been studied for many years in the context of its positive effects on heart function and its increased tolerance to ischemia-reperfusion (I/R) injury. This Master thesis describes the role of Akt kinase in the mechanisms leading to myocardial protection against I/R injury using the model of adaptation to chronic normobaric hypoxia (CNH). The hearts from male Wistar rats, that were kept in normoxic or hypoxic conditions (O2 0.1) for the period of 3 weeks, were retrogradely perfused by oxygenated Krebs-Henseleit solution and then subjected to 10 min of ischemia and 10 min of reperfusion. Samples prepared from left ventricles (LV) of experimental hearts were later used for protein analyses. The adaptation to CNH leads to increased phosphorylation of Akt kinase on Ser473, but it did not affect the phosphorylation on Thr308 nor the total protein level of Akt. A significant increase in Bcl-2/Bax ratio was also observed in hearts adapted to CNH. This Master thesis further elucidates, how Akt signaling pathway and its activation are affected by short...
|
|
|
The role of PGC-1α during the development of a cardioprotective phenotype in a rat adapted to mild cold
Bajsová, Barbora ; Žurmanová, Jitka (advisor) ; Szeiffová Bačová, Barbara (referee)
Cold exposure elicits a thermoregulatory response in an organism. If the cold stimulus is sufficient, there is increased heat generation by shivering thermogenesis. Under prolonged action of the cold stimulus, shivering thermogenesis is replaced by non-shivering thermogenesis. Non-shivering thermogenesis in the rat takes place predominantly in brown adipose tissue (BAT), where the uncoupling protein 1 (UCP1) is activated in mitochondria under the control of adrenergic signaling. The activity of UCP1 is crucial for heat production. The coactivator PGC-1α plays an important role in mitochondrial biogenesis and in the energy metabolism of BAT and heart, and its function is associated with cardioprotection. Recently, the cardioprotective effects of mild cold adaptation at 8±1 řC were discovered in our laboratory, which reduced the size of ischemia-reperfusion injury without negative side effects. However, the molecular nature of the events induced by adaptation to mild cold is unknown neither in BAT nor in the heart itself. Therefore, the aims of the thesis were 1) to characterize the development of BAT at the level of expression of selected proteins and mitochondrial markers during acute cold exposure and chronic cold adaptation with subsequent recovery and 2) to determine the role of PGC-1α and...
|
|
|
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
|
|
|
Antioxidant system in hypoxic heart
Sotáková, Dita ; Žurmanová, Jitka (advisor) ; Kalous, Martin (referee) ; Babula, Petr (referee)
The cardiovascular disease, particularly acute myocardial infarction, is the most common cause of death worldwide. It is well documented that adaptation to chronic hypoxia increases resistance to ischemia-reperfusion (I/R) injury in heart tissue. Reactive oxygen species (ROS) play an important signalling role by the activation of the protective pathways during I/R, although, the excess of ROS during reperfusion leads to cardiac tissue injury. As the cellular antioxidant system is responsible for the maintenance of redox homeostasis, the main aim of this thesis was to investigate the relationship between myocardial tolerance to I/R injury and regulation of main components of antioxidant systems, related transcription factors and their target genes in protective and non- protective regimens of chronic hypoxia. We found differences in cardioprotective phenotype in rats exposed to three regimens of chronic normobaric hypoxia (FiO2 0.1, 3 weeks). The adaptation to continual (CNH) and intermittent (CNH-8; 8 h/day) regimen of hypoxia increased myocardial resistance to I/R damage, whereas 1-hour daily interruption of hypoxic adaptation (INH-23) abolished cardioprotective effect and decreased the ratio of reduced and oxidized glutathione (GSH/GSSG). Both cardioprotective regimens significantly increased...
|
|
| |
|
|
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)
|
|
| |
|
|
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.
|
guest ::
