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Adenosine metabolism and its role in cell physiology
Neumannová, Kateřina ; Novotný, Jiří (advisor) ; Hansíková, Jana (referee)
Adenosine is not just a major component of important molecules such as ATP, RNA or cAMP, but also has its own signaling function. Therefore, its extracellular level is strictly maintained by balance in its formation, degradation and transport. Both inside and outside the cell adenosine is formed mainly through degradation of ATP and is eliminated by two enzymes, adenosine kinase and adenosine deaminase. Transport of adenosine through the cell membrane is provided by nucleoside transporters, which are either equilibrative or concentrative according to the mechanism of transfer. All three processes described above contribute to maintaining adenosine level under normal conditions and its increase in pathological situations. Extracellular adenosine as a signal molecule binds to adenosine receptors (subtypes A1, A2A, A2B, A3) that affect many cellular signaling pathways via G-proteins. By these pathways adenosine regulates energy homeostasis, controls the function of various organs and also modulates the nervous and immune system and thus it may participate in a number of pathological processes. Pharmacological affecting of specific adenosine receptors or enzymes involved in its metabolism can serve as an effective therapy. Some drugs based on this system are already in use, others are being tested, and many...
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Maturation of AMPK in skeletal muscle during early postnatal development
Hansíková, Jana ; Janovská, Petra (advisor) ; Kalous, Martin (referee)
AMP-activated protein kinase (AMPK) is an important metabolic sensor in eukaryotic organisms and it plays an important role in regulating energy homeostasis, at both the cells and the whole organism. AMPK controls glucose and lipid metabolism by direct stimulation of enzymes or by long term stimulation of the gene expression of energy metabolism. Skeletal muscles significantly contribute to the total body weight and metabolic rate and to the maintenance of glucose homeostasis. Due to the ability of the muscle to increase energy expenditure to 95% of whole-body energy expenditure, could be the proper development and programming of metabolism in the early postnatal period crucial for the further development of the organism in adulthood. Early postnatal development leads to substantial changes in energy requirements of the body and this suggests the significant involvement of AMPK in this period. The aim of this thesis was to study the activity and expression of isoforms of the catalytic subunit of AMPK in skeletal muscle during early postnatal development of both mouse strains A/J and C57BL/6 that differ in the development of diet-induced obesity. The next task was to analyze the expression of selected genes involved in energy metabolism - GLUT4, PGC-1α and UCP3 that AMPK regulates. It was found that the...
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Adenosine metabolism and its role in cell physiology
Neumannová, Kateřina ; Novotný, Jiří (advisor) ; Hansíková, Jana (referee)
Adenosine is not just a major component of important molecules such as ATP, RNA or cAMP, but also has its own signaling function. Therefore, its extracellular level is strictly maintained by balance in its formation, degradation and transport. Both inside and outside the cell adenosine is formed mainly through degradation of ATP and is eliminated by two enzymes, adenosine kinase and adenosine deaminase. Transport of adenosine through the cell membrane is provided by nucleoside transporters, which are either equilibrative or concentrative according to the mechanism of transfer. All three processes described above contribute to maintaining adenosine level under normal conditions and its increase in pathological situations. Extracellular adenosine as a signal molecule binds to adenosine receptors (subtypes A1, A2A, A2B, A3) that affect many cellular signaling pathways via G-proteins. By these pathways adenosine regulates energy homeostasis, controls the function of various organs and also modulates the nervous and immune system and thus it may participate in a number of pathological processes. Pharmacological affecting of specific adenosine receptors or enzymes involved in its metabolism can serve as an effective therapy. Some drugs based on this system are already in use, others are being tested, and many...
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Maturation of AMPK in skeletal muscle during early postnatal development
Hansíková, Jana ; Janovská, Petra (advisor) ; Kalous, Martin (referee)
AMP-activated protein kinase (AMPK) is an important metabolic sensor in eukaryotic organisms and it plays an important role in regulating energy homeostasis, at both the cells and the whole organism. AMPK controls glucose and lipid metabolism by direct stimulation of enzymes or by long term stimulation of the gene expression of energy metabolism. Skeletal muscles significantly contribute to the total body weight and metabolic rate and to the maintenance of glucose homeostasis. Due to the ability of the muscle to increase energy expenditure to 95% of whole-body energy expenditure, could be the proper development and programming of metabolism in the early postnatal period crucial for the further development of the organism in adulthood. Early postnatal development leads to substantial changes in energy requirements of the body and this suggests the significant involvement of AMPK in this period. The aim of this thesis was to study the activity and expression of isoforms of the catalytic subunit of AMPK in skeletal muscle during early postnatal development of both mouse strains A/J and C57BL/6 that differ in the development of diet-induced obesity. The next task was to analyze the expression of selected genes involved in energy metabolism - GLUT4, PGC-1α and UCP3 that AMPK regulates. It was found that the...
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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.
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