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Introduction of Western blotting method for detection of AMPK cascade activation in LS174T cell line
Dubecká, Michaela ; Pávek, Petr (advisor) ; Nachtigal, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Michaela Dubecká Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Introduction of Western blotting method for detection of AMPK cascade activation in LS174T cell line LKB1/AMPK is the main cellular energetic pathway, which acts as the sensor of various extra- and intracellular signals. In response to the signals, it regulates energy metabolism and the maintenance of cellular homeostasis, so its major role lies in the survival, growth and development of the whole organism. This pathway is of significant importance because it has the potential to suppress tumoral progress in the cell. Metformin, the widely used drug in the treatment of type 2 diabetes, exerts a significant antitumour activity. However, the direct mechanism of metformin's action is still unknown. Metformin induces cellular stress similar to the metabolic stress via inhibiting mitochondrial respiratory chain complex I, which results in an increase of AMP levels in plasma. AMP then binds to the AMPKγ subunit, so metformin mediates the activation of AMPK. AMPK is suddenly phosphorylated on Thr172 of the AMPKα kinase domain via LKB1, which mediates the downregulation of many downstream kinases. The...
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Study of interactions of polyfenolic compounds on nuclear receptors
Dubecká, Michaela ; Pávek, Petr (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Supervisor: Title of diplova thesis: Mgr. Michaela Dubecká Prof. PharmDr. Petr Pávek, Ph.D. Study of interactions of polyfenolic compounds on nuclear receptors The farnesoid X receptor (FXR) is a receptor of primary bile acids in the liver and intestine. FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of cholestasis, metabolic syndrome and diabetes, fatty liver disease, cholesterol gallstone disease and intestinal inflammation. Furthermore, FXR plays an important role in the gut-liver axis feedbacks regulating lipid and glucose homeostasis. The apical sodium dependent bile acid transporter (ASBT; SLC10A2) is a bile acid transporter localized to the apical surface of the terminal ileal enterocytes. ASBT plays an important role in the reabsorption of bile acids in the ileum. In the liver, the hepatocytes take up the bile acids by the sinusoidal sodium-dependent taurocholate co-transporting polypeptide (NTCP; SLC10A1). ASBT and NTCP are regulated in the ileum and liver through FXR receptor by bile acids to control bile acids pool. In the current study, we analyzed whether anthocyanins or...
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Study of interactions of polyfenolic compounds on nuclear receptors
Dubecká, Michaela ; Pávek, Petr (advisor) ; Filipský, Tomáš (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Supervisor: Title of diplova thesis: Mgr. Michaela Dubecká Prof. PharmDr. Petr Pávek, Ph.D. Study of interactions of polyfenolic compounds on nuclear receptors The farnesoid X receptor (FXR) is a receptor of primary bile acids in the liver and intestine. FXR has been shown to be the master transcriptional regulator of several entero-hepatic metabolic pathways with relevance to the pathophysiology of cholestasis, metabolic syndrome and diabetes, fatty liver disease, cholesterol gallstone disease and intestinal inflammation. Furthermore, FXR plays an important role in the gut-liver axis feedbacks regulating lipid and glucose homeostasis. The apical sodium dependent bile acid transporter (ASBT; SLC10A2) is a bile acid transporter localized to the apical surface of the terminal ileal enterocytes. ASBT plays an important role in the reabsorption of bile acids in the ileum. In the liver, the hepatocytes take up the bile acids by the sinusoidal sodium-dependent taurocholate co-transporting polypeptide (NTCP; SLC10A1). ASBT and NTCP are regulated in the ileum and liver through FXR receptor by bile acids to control bile acids pool. In the current study, we analyzed whether anthocyanins or...
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Introduction of Western blotting method for detection of AMPK cascade activation in LS174T cell line
Dubecká, Michaela ; Pávek, Petr (advisor) ; Nachtigal, Petr (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Michaela Dubecká Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Introduction of Western blotting method for detection of AMPK cascade activation in LS174T cell line LKB1/AMPK is the main cellular energetic pathway, which acts as the sensor of various extra- and intracellular signals. In response to the signals, it regulates energy metabolism and the maintenance of cellular homeostasis, so its major role lies in the survival, growth and development of the whole organism. This pathway is of significant importance because it has the potential to suppress tumoral progress in the cell. Metformin, the widely used drug in the treatment of type 2 diabetes, exerts a significant antitumour activity. However, the direct mechanism of metformin's action is still unknown. Metformin induces cellular stress similar to the metabolic stress via inhibiting mitochondrial respiratory chain complex I, which results in an increase of AMP levels in plasma. AMP then binds to the AMPKγ subunit, so metformin mediates the activation of AMPK. AMPK is suddenly phosphorylated on Thr172 of the AMPKα kinase domain via LKB1, which mediates the downregulation of many downstream kinases. The...
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