CELLULAR AND MOLECULAR BIOLOGY OF LIPOPROTEIN METABOLISM

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This application represents a continuation of a Program Project with an overall theme to study the interaction of lipoproteins with cells and tissues. The major emphasis of this research focuses on I) the role of apoproteins in determining the recognition and fate of lipoproteins, 2) the kinetics and mechanisms of any consequent movement of proteins and lipid between cells and lipoproteins, and 3) the cellular storage and metabolism of lipids. The goal of these studies is to provide basic information on the mechanisms involved in the metabolism of lipids and lipoproteins which will advance our understanding of the events leading to the formation and regression of the atherosclerotic plaque. This application consists of four closely related projects supported by three Core Laboratories: 1) Administrative/Central Core, 2) Tissue Culture Core, and 3) Lipoprotein Core. Project 1 proposes studies on the synthesis and metabolism of lipoproteins with particular emphasis on apoprotein B. The investigations will use experimental systems ranging from whole animals to subcellular fraction. Project 2 consists of studies which will focus on the movement of lipid between cells in culture and lipoproteins, and the influence of enzymatic modification of lipoproteins on this movement. These studies will utilize cultured cells, subcellular fractions and a variety of molecules including enzymes, lipoproteins and lipids. Project 3 proposes studies that will elucidate some structure-function relationships in lipoproteins; of particular concern are the mechanisms of cholesterol movement and the interaction between lipids and proteins within lipoproteins. In this project, experiments are proposed that will use a variety of experimental approaches ranging from cultured cells to the interaction of individual molecules as viewed by physical methods. Project 4 details a number of experiments which will address the interaction of lipoproteins, particularly chylomicrons, with cells and tissue, with emphasis on transport of retinol and retinyl esters. Experimental systems in this Project range over the entire spectrum from whole animals to In Vitro studies on enzymes and lipid molecules. 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 disciplines encompassed by these investigators include biochemistry, physiology, physical chemistry, cell and molecular biology and nutrition.