|
|
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.
|
|
|
Importance of AMP-activated protein kinase in the regulation of energy metabolism of mammals
Hansíková, Jana ; Janovská, Petra (advisor) ; Žurmanová, Jitka (referee)
Enzyme AMP-activated protein kinase (AMPK) is a serin/threonin protein kinase, its main role is in energy regulation at both on the cellular and whole body levels. As a stress sensor controls the oxidation of fatty acid, transport and uptake of glucose uptake into cell, gluconeogenesis and other metabolic pathway in tissue such as liver, skeletal muscle and adipose tissue including hypothalamic central regulation of food intake and energy expenditure. Regulation of AMPK on whole-body level is coordinated by a variety of hormones (adipokines) secreted by adipose tissue. Leptin is one of key adipokines associated with the efect of AMPK . Effects of leptin are linked to both programming the metabolism in the perinatal period and with important regulations in adult metabolism. Data about development of AMPK in the hypothalamus and peripheral tissues in the perinatal period are still rare. Considering to the key role of AMPK in mediation of central regulation of leptin in the hypothalamus and metabolic effects of leptin in muscle, further research to expand knowledge in this area is required.
|
|
|
Calcium homeostasis and modulation of nociceptive synaptic transmission
Sojka, David ; Paleček, Jiří (advisor) ; Žurmanová, Jitka (referee) ; Krůšek, Jan (referee)
2 SUMMARY OF THE THESIS This study was designed to improve our knowledge regarding mechanisms of nociceptive signaling at spinal cord level. One of the forms of spinal cord synaptic transmission modulation is central sensitization, a manifestation of synaptic plasticity at spinal cord level, which was found to be present at many chronic pain syndromes. This study deals mainly with a development of calcium imaging technique with a final goal to study mechanisms of central sensitization in vitro on population of dorsal horn neurons. We have analyzed synaptically evoked intracellular Ca changes as a result of dorsal root stimulation in a superficial dorsal horn area in spinal cord slices and found two types of Ca responses: one synchronized with electrical stimulation and a second one, delayed response due to Ca release from internal stores. The delayed Ca release was not previously shown to be present in these neurons and it was not dependent on activation of ionotropic glutamatergic receptors, suggesting involvement of metabotropic receptor pathway. The presence of this delayed type of Ca response could have a significant role in the induction of some types of chronic pain syndromes since intracellular calcium increase is thought to be a key trigger point in spinal cord neurons sensitization. An important...
|
|
|
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...
|
|
| |
|
| |
|
| |
|
|
The entry of lead into the brain after experimental administration of lead acetate
Patková, Jana ; Žurmanová, Jitka (referee) ; Vojtíšek, Maxmilián (advisor)
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...
|
|
|
A fluorescence microscopy study on free radicals engagement in the vascular wall remodelling under various experimental conditions
Tomšů, Eva ; Wilhelm, Jiří (advisor) ; Žurmanová, Jitka (referee)
Free radicals are engaged in many cellular actions. Recently, free radicals of versatile kinds reveal to be engaged in changes of the vascular wall composition i.e. in its remodelling. Reactive oxygen species (ROS), mostly of radical nature, are engaged it these actions actively. There are many fluorescent dyes detecting ROS intracellularly. We use mostly dichlorofluorescin, dihydrorhodamine, and dihydroethidium that differ in specificity to individual kinds of ROS. Preliminary studies in our laboratory revealed the opportunity to trace changes of the vascular wall composition during the neonatal developmental period of the laboratory rats heart using above mentioned substances. Powered by TCPDF (www.tcpdf.org)
|
|
| |
guest ::
