Thesis (Ph. D. in Biological Sciences)--Vanderbilt University, May 2007. / Title from title screen. Includes bibliographical references.

No description available.

Thesis (Ph. D.)--University of Missouri-Columbia, 2006. / "May 2006" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.

Two studies were conducted to determine how HDL cholesteryl ester and apoprotein catabolism might contribute to the observed hypercholesterolemia of copper-deficient rats. Weanling male Sprague-Dawley rats were divided into two dietary treatments; copper-adequate (control, 5-7 mg Cu/kg diet) and copper-deficient (0.6-0.8 mg Cu/kg diet). Deionized water and diet were provided ad libitum. Dietary copper deficiency resulted in enlarged intravascular pools of HDL cholesteryl esters and total protein. HDL were isolated from rats of both treatment groups, radiolabeled, and injected into animals of the respective groups. In Study I, HDL apoproteins were labeled by iodination, whereas HDL in Study II were doubly labeled by additionally incorporating into the particle core [³H]cholesteryl linoleyl ether, which served as a nondegradable analog of HDL cholesteryl ester. At specific time intervals up to 12 hours after injection, blood and tissue samples were removed and analyzed for radioactivity. Plasma disappearance curves indicated that HDL cholesteryl esters were preferentially catabolized 1.6-fold faster than HDL protein in controls and 2.5-fold faster in copper-deficient animals. Clearance of individual apoproteins did not occur at significantly different rates in either treatment group. Absolute mass removal of HDL cholesteryl ester and total protein from the plasma was significantly increased in copper-deficient rats. Virtually all of the increased removal of HDL cholesteryl ester was attributed to the liver, whereas most of the increased uptake of HDL protein was attributed to the bulk tissues and not the liver. Since previous studies indicate that copper deficiency may not result in increased cholesterol excretion, these data suggest that cholesteryl esters delivered to the liver of copper-deficient rats are possibly reassembled into new HDL particles at an increased rate. The observed hypercholesterolemia in this animal model, then, appears to be the result of an imbalance in the net flux of cholesterol between the tissues and the plasma.

Two studies were designed to investigate the time course development of enlarged plasma volume and cholesterol pool size in copper (Cu)-deficient rats as well as influence of Cu deficiency on the lipid composition of lipoproteins. Rats were randomly assigned to three dietary Cu treatments (deficient, marginal, and adequate) in the Study I and two dietary Cu treatments (deficient and adequate) in Study II. Enlargement of plasma volume and cholesterol pool size were established prior to the increase in plasma cholesterol concentration. Cu concentration was decreased, whereas iron and zinc concentrations were increased in the organs of Cu-deficient and Cu-marginal rats. The plasma pool size of VLDL triglyceride was elevated 6-fold, protein and phospholipid were unaltered, and cholesterol was reduced 36%. The plasma pool size of lipid and protein components of HDL and LDL fractions were markedly elevated in Cu-deficient rats.

No abstract available