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Regulation of cholesterol metabolism in hepatocytes
Ziková, Kateřina ; Vlachová, Miluše (advisor) ; Zlatohlávek, Lukáš (referee)
This thesis summarizes current data about cholesterol metabolism and its regulation in the liver. First part describes cholesterol transport among tissues by lipoproteins. Second part of this work deals with description of metabolic pathways of cholesterol conversion - how the cells obtain and metabolise cholesterol. Almost all cells can synthesize cholesterol or take it up from the circulation. The cells dispose of abundant cholesterol by several mechanisms - they convert cholesterol to cholesteryl esters that can be stored in lipid droplets; they turn cholesterol into oxysterols that can escape easier from the cell; or they export cholesterol through ATP-binding cassette (ABC) transporters. Specialized tissues (adrenal, gonads) transform cholesterol to steroid hormones. However, only the liver can remove cholesterol from the body in physiologically significant amount - it secretes cholesterol into the bile either directly or after conversion to bile acids. Third section deals with regulation of cholesterol metabolism in hepatocyte. Three transcription factors - sterol regulatory element binding protein (SREBP), liver X receptor (LXR), and farnesoid X receptor (FXR) - play the main role in regulation. Their activities are determined by concentration of cellular cholesterol or its metabolites -...
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Viral hepatitis: novel insights and novel therapeutic interventions.
Davidovová, Eva ; Pávek, Petr (advisor) ; Trejtnar, František (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Bc. Eva Davidovová Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Viral hepatitis: novel insights and novel therapeutic interventions. Viral hepatitis is a well-known worldwide problem. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are characterized by the development of serious complications, especially with regard to the transition to the chronic stage of the disease, associated with the development of fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Interactions between viruses and host cells are quite complicated and not always fully understood. In general, the infection cycle of viruses is a multi-step process. A closer understanding of the entire life cycle of the virus is a major prerequisite for the invention of effective drugs. Viral hepatitis B and C have long been treated mainly with interferon alfa. Ribavirin was later added to HCV treatment and nucleoside / nucleotide analogs (NA) were introduced for HBV. Interferon was later pegylated to improve its properties. However, these drugs did not provide sufficient efficacy and were additionally associated with a number of side effects. It is precisely because of these disadvantages of the current...
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Regulation of cholesterol metabolism in hepatocytes
Ziková, Kateřina ; Vlachová, Miluše (advisor) ; Zlatohlávek, Lukáš (referee)
This thesis summarizes current data about cholesterol metabolism and its regulation in the liver. First part describes cholesterol transport among tissues by lipoproteins. Second part of this work deals with description of metabolic pathways of cholesterol conversion - how the cells obtain and metabolise cholesterol. Almost all cells can synthesize cholesterol or take it up from the circulation. The cells dispose of abundant cholesterol by several mechanisms - they convert cholesterol to cholesteryl esters that can be stored in lipid droplets; they turn cholesterol into oxysterols that can escape easier from the cell; or they export cholesterol through ATP-binding cassette (ABC) transporters. Specialized tissues (adrenal, gonads) transform cholesterol to steroid hormones. However, only the liver can remove cholesterol from the body in physiologically significant amount - it secretes cholesterol into the bile either directly or after conversion to bile acids. Third section deals with regulation of cholesterol metabolism in hepatocyte. Three transcription factors - sterol regulatory element binding protein (SREBP), liver X receptor (LXR), and farnesoid X receptor (FXR) - play the main role in regulation. Their activities are determined by concentration of cellular cholesterol or its metabolites -...
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