National Repository of Grey Literature 2 records found  Search took 0.01 seconds. 
Genetic determination of cholesterolemia regulation
Vlachová, Miluše ; Kovář, Jan (advisor) ; Vrablík, Michal (referee) ; Kazdová, Ludmila (referee)
Most types of hypercholesterolemia are of polygenic origin. Some genes related to hypercholesterolemia are known, although all genes responsible for cholesterolemia regulation have not been characterised yet. To identify these new genes, animal models with spontaneous defects in cholesterol metabolism could be very useful. Moreover, a number of variations and polymorphisms have been found to influence blood cholesterol levels in humans. Some may also affect cholesterolemia responsiveness to dietary fat. The Prague hereditary hypercholesterolemic (PHHC) rat is a unique model of hypercholesterolemia induced by dietary cholesterol alone (without administration of cholic acid or thyrotoxic drugs). It exhibits modestly increased cholesterolemia when fed chow and responds to a diet containing cholesterol with a several-fold increase of cholesterolemia to concentrations comparable to those observed in hypercholesterolemic patients. Hypercholesterolemia in this model is characterised by accumulation of very low density lipoproteins (VLDL) and intermediate density lipoproteins (IDL) enriched by cholesterol. In an experiment with tyloxapol (an inhibitor of lipoprotein lipase) we found that PHHC rats on a cholesterol diet incorporated twice as much cholesterol into VLDL as Wistar rats, although liver...
The role of cholesterol 7alpha-hydroxylase in regulation of cholesterolemia
Cejpková, Monika ; Kovář, Jan (advisor) ; Leníček, Martin (referee)
The aim of the theses is to characterize the mechanism that participate in the regulation of activity of cholesterol 7α-hydroxylase (CYP7A1) - the key enzyme of classical pathway of bile acids synthesis. The function and metabolism of cholesterol and bile acid is described at the beginning. Cholesterol is a substrate for CYP7A1 and bile acids are produced in the reaction catalyzed by the enzyme. The other parth of theses is dedicated to feedback inhibition of CYP7A1 by bile acids and describes particular regulatory pathways involved. The crucial factors for CYP7A1 expression are bile acids response elements (BARE) in the promoter of CYP7A1 gene. Central role is played by farnesoid X receptor activated by bile salts that induces expression of protein called small heterodimer partner (SHP) in the liver. SHP interacts with trancription factors in BARE and inhibits CYP7A1 transcription. In the instestine FXR induces fibroblast growth factor 19 (FGF19) that activates signalling pathways leading to inhibition of CYP7A1 in the liver. The activity of CYP7A1 can be regulated independently of FXR - there is a role for hormones (insulin, glucagon), glucose, activation of proinflammatory cytokines and other nuclear receptors (pregnane X receptor and vitamin D receptor), that participate in protection of the...

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