CELLULAR AND MOLECULAR BIOLOGY OF LIPOPROTEIN METABOLISM

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This application represents a continuation of a Program Project with the overall theme to study the interaction of lipoproteins with cells and tissues, and the subsequent metabolism of lipids within cells. The basic information that will be gained from the studies will be particularly relevant to the progression and regression of the atherosclerotic plaque. The major emphasis of this research focuses on: 1) interaction of lipids with apoproteins, 2) cellular uptake, metabolism and release of lipids, and 3) relationships between cellular lipid metabolism and the synthesis and secretion of lipid/protein complexes. This Program Project consists of five closely related projects: Project 1 proposes to study the processes involved in hepatic synthesis and secretion of plasma lipoproteins in the rat. Particular emphasis is placed on the links between hepatic triglyceride synthesis and secretion of plasma lipoproteins. Project 2 represents a continuation of studies on the flux of cholesterol between lipoproteins and cells in culture. Emphasis is placed on estab- lishing the mechanism(s) and regulation of movement of cholesterol between HDL and cultures cells. Project 3 extends previous work on the structure of lipoproteins to a study on the conformations of apoproteins in order to obtain greater understanding of the apoprotein-lipid interactions in lipoproteins. Project 4 will continue and expand previous studies on the cellular metabolism of retinol and retinyl esters, using tissue culture cells as the primary experimental system. These studies will establish the relationship between retinol and retinyl ester uptake, intracellular esterification and hydrolysis, and secretion. Project 5 will focus on the intracellular metabolism of free and esterified cholesterol, using a variety of types of cells in culture. Emphasis is placed on the factors involved in the deposition and clearance of esterified cholesterol from cells. The group of investigators comprising this Program Project share similar interests and goals in lipid and lipoprotein metabolism while providing broad scientific expertise. The scientific discipline encompassed by these investigators include biochemistry, physiology, physical chemistry, cell and molecular biology and nutrition. The five scientific projects are supported by three core laboratories: 1) Administrative/Central Service Core, 2) Tissue Culture Core and 3) Lipoprotein Core.