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Articles 1 - 9 of 9
Full-Text Articles in Molecular Biology
Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen
Metoprolol Disrupts Sterol Biosynthesis Through Inhibition Of 7-Dehydrocholesterol Reductase (Dhcr7), Luke B. Allen
Theses & Dissertations
Cholesterol is essential for life. It is particularly important in the brain as it relies on de novo synthesis of cholesterol following the formation of the blood brain barrier (BBB). As such, disrupting sterol biosynthesis during neurodevelopment can have devastating outcomes. The most common post-lanosterol sterol biosynthesis disorder, Smith-Lemli-Opitz Syndrome, arises from a faulty DHCR7 enzyme. DHCR7 has also been shown to be inhibited by several psychotropic medications. Here we assess six beta-blockers and their effects on sterol biosynthesis in vitro. Two beta-blockers, metoprolol and nebivolol strongly inhibit DHCR7 in four separate in vitro models of both mouse and …
Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen
Cholesterol Biosynthesis In The Nervous System With An Emphasis On Desmosterolosis, Luke Allen
Theses & Dissertations
Cholesterol biosynthesis is integral to proper neurodevelopment due to the reliance on de novo synthesis of cholesterol in the brain. Disruptions in this process have devastating outcomes for human life characterized by several phenotypic manifestations concomitant with developmental delay. The cholesterol biosynthesis disorder desmosterolosis is an extremely rare disorder with a severe clinical phenotype, however, the models used to study this disease are not well characterized. In addition to genetic disruptions in cholesterol biosynthesis, pharmacological perturbation is an understudied side effect of many commonly prescribed drugs. Here we present a characterization of the sterol profile of the mouse model of …
Abcg5 And Abcg8: More Than A Defense Against Xenosterols, Shailendra B. Patel, Gregory A. Graf, Ryan E. Temel
Abcg5 And Abcg8: More Than A Defense Against Xenosterols, Shailendra B. Patel, Gregory A. Graf, Ryan E. Temel
Pharmaceutical Sciences Faculty Publications
The elucidation of the molecular basis of the rare disease, sitosterolemia, has revolutionized our mechanistic understanding of how dietary sterols are excreted and how cholesterol is eliminated from the body. Two proteins, ABCG5 and ABCG8, encoded by the sitosterolemia locus, work as obligate dimers to pump sterols out of hepatocytes and enterocytes. ABCG5/ABCG8 are key in regulating whole-body sterol trafficking, by eliminating sterols via the biliary tree as well as the intestinal tract. Importantly, these transporters keep xenosterols from accumulating in the body. The sitosterolemia locus has been genetically associated with lipid levels and downstream atherosclerotic disease, as well as …
Engineering Probes To Detect Cholesterol Accessibility On Membranes Using Perfringolysin O, Benjamin B. Johnson
Engineering Probes To Detect Cholesterol Accessibility On Membranes Using Perfringolysin O, Benjamin B. Johnson
Doctoral Dissertations
Cholesterol is an essential component of mammalian cell membranes and it is important to regulate the structure and function of lipid bilayers. Changes in cholesterol levels are involved in many physiological and pathological events such as the formation of arterial plaques, viral entry into cells, sperm capacitation, and receptor organization. Determination of cholesterol trafficking and distribution is essential for understanding how cells regulate cholesterol. A key factor in the regulation of cholesterol is cholesterol accessibility. Through it interactions in the membrane, cholesterol is sequestered below the surface of the membrane. Based on the composition of the membrane, a certain amount …
Validation Of A Novel Hypothesis Of Generating Foam Cells By Its Use To Study Reverse Cholesterol Transport, Bhaswati Sengupta
Validation Of A Novel Hypothesis Of Generating Foam Cells By Its Use To Study Reverse Cholesterol Transport, Bhaswati Sengupta
Electronic Theses and Dissertations
Generation of foam cells, an essential step for reverse cholesterol transport (RCT) studies, uses the technique of receptor dependent macrophage loading with radiolabeled acetylated Low Density Lipoprotein (Ac-LDL). In this study, we used the ability of a biologically relevant detergent molecule, Lysophosphatidylcholine (Lyso PtdCho), to form mixed micelles with cholesterol or cholesteryl ester (CE) to generate macrophage foam cells. Fluorescent or radiolabelled cholesterol / Lyso PtdCho mixed micelles were prepared and incubated with RAW 264.7 or mouse peritoneal macrophages. Results showed that such micelles were quite stable at 4°C and retained the solubilized cholesterol during one month storage. Macrophages incubated …
Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi
Molecular Mechanisms Underlying The Early Life Programming Of The Liver, Gurjeev Sohi
Electronic Thesis and Dissertation Repository
Clinical studies have demonstrated that intrauterine growth restriction (IUGR) offspring, faced with a nutritional mismatch postpartum, have an increased risk of developing the metabolic syndrome. The maternal protein restriction (MPR) rat model has been extensively studied to investigate the adverse effects of a nutritional mismatch in postnatal life of IUGR offspring. Previous studies have demonstrated that MPR leads to impaired function of the liver, an important metabolic organ. However the underlying mechanisms which predispose these offspring to the metabolic syndrome remain elusive. In the following studies, low protein diet during pregnancy and lactation led to IUGR offspring with decreased liver …
Molecular Regulators Of Post-Golgi Vldl Transport Vesicle (Pg-Vtv) Biogenesis, Aladdin Riad
Molecular Regulators Of Post-Golgi Vldl Transport Vesicle (Pg-Vtv) Biogenesis, Aladdin Riad
Electronic Theses and Dissertations
Amongst its numerous functions, the liver is responsible for the synthesis and secretion of very low-density lipoprotein (VLDL). VLDL particles play the important role of facilitating the transport of lipids within the aqueous environment of the plasma; yet high plasma concentrations of these particles result in the pathogenesis of atherosclerosis, while low VLDL secretion from the liver results in hepatic steatosis. VLDL synthesis in the hepatocyte is completed in the Golgi apparatus, which serves as the final site of VLDL maturation prior to its secretion to the bloodstream. The mechanism by which VLDL’s targeted transport to the plasma membrane is …
Insights Into Hepatic Alpha-Fetoprotein Gene Regulation During Liver Development And Disease, Erica Leigh Clinkenbeard
Insights Into Hepatic Alpha-Fetoprotein Gene Regulation During Liver Development And Disease, Erica Leigh Clinkenbeard
Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics
The liver is an essential organ for cholesterol homeostasis. If this process becomes dysregulated, cardiovascular disease (CVD) develops. Zinc-fingers and homeoboxes 2 (Zhx2) as an important hepatic gene regulator and contributes to CVD. BALB/cJ mice, with mutant Zhx2 allele, have fewer atherosclerotic plaques compared to other strains on a high fat diet. In my dissertation, I focused on the liver phenotype in BALB/cJ mice on a high-fat diet and found increased liver damage compared to wild-type Zhx2 mice. These data indicates that reduced Zhx2 in the liver leads to CVD resistance, but increases liver damage. Therefore, Zhx2 has an important …
Biotransformation Of Bile Acids, Cholesterol And Steroids. Chapter 13 In: The Ecology And Physiology Of Gastrointestinal Microbes. Vol. 1, New York, Chapman And Hall., Stephen Baron, Phillip B. Hylemon
Biotransformation Of Bile Acids, Cholesterol And Steroids. Chapter 13 In: The Ecology And Physiology Of Gastrointestinal Microbes. Vol. 1, New York, Chapman And Hall., Stephen Baron, Phillip B. Hylemon
Biology Faculty Scholarship
No abstract provided.