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Pharmacological interventions of nuclear receptors in diabettes mellitus
Draský, Jakub ; Pávek, Petr (advisor) ; Bárta, Pavel (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Jakub Draský Supervisor: prof. PharmDr. Petr Pávek, Ph.D. Title of diploma thesis: Pharmacological influence of nuclear receptors in diabetes mellitus therapy Nuclear receptors belong to the superfamily of transcription factors, their main functions include regulating the expression of target genes. In my work I focused mainly on the group of orphan receptors, namely the pregnane X receptor (PXR) and the constitutive androstane receptor (CAR). A common feature of these receptors is their activation by a specific ligand. Both CAR and PXR have an essential function as biological sensors of hydrophobic xenobiotics when they induce enzymes I and II. phase of metabolism. They are also essential in the regulation of gluconeogenesis, insulin response, adipogenesis, cholesterol homeostasis, fatty acids, triglycerides and glycogen. The aim of this experimental work was to introduce a luciferase reporter assay method for two DNA constructs containing the promoter region of the PEPCK and CYP7A1 genes. We used the known agonist rifampicin and the antagonist SPA70 to activate/deactivate PXR. We used CITCO as a CAR receptor agonist. We first verified the functionality of the luciferase reporter gene assay...
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The role of FAT/CD36 trasporter in the pathophysiology of heart
Kovalčíková, Jana ; Nováková, Olga (advisor) ; Wasková, Petra (referee)
1. Abstract FAT/CD36 is an 88 kDa glycoprotein that plays a key role in the transport of long- chain fatty acids (LCFA) through the plasma membrane in heart, skeletal muscle and adipose tissue. It participates in the fatty acids (FA) transport together with other membrane proteins, which are fatty acid transport proteins (FATP1-6), the plasma membrane fatty acid binding protein (FABPpm) and cytosolic fatty acid binding protein (FABPc). In cardiac tissue are, except FAT/CD36, only represented FABPpm, FATP1 and 6 and heart type of FABPc, referred to as H-FABPc. In addition to this protein mediated FA transport, FA are already known to be transported by passive diffusion. The cell expression of FAT/CD36 is regulated by nuclear peroxisome proliferators- activated receptor (PPAR), in the heart primarily by PPAR- . Inactive FAT/CD36 is found in intracellular depots, while active FAT/CD36 is present on the plasma membrane in lipid rafts. The two most known pathways regulating the FAT/CD36 translocation from the depots to the membrane are the insulin signalling pathway, which involves the activation of the enzyme phosphatidyl-inositol-3-kinase (PI3K) and cardiac contraction activated cascade, which activates adenosinmonophosphate kinase (AMP kinase). Furthermore, FAT/CD36 can as well be regulated by ubiquitination...
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