APOLIPOPROTEIN METABOLISM: REGULATION AND FUNCTION

这个项目的中心主题是调控

The central theme of this program project is the regulation of apolipoprotein metabolism and its physiologic role in lipid and lipoprotein homeostasis. To achieve this goal, we organized a multi-disciplinary approach involving physiology, biochemistry, immunochemistry, and cell biology, employing both in vivo and in vitro techniques. We propose the following broad areas of investigation: 1. To study peripheral lymph lipoprotein metabolism by: a) further characterization of "interstitial" lipoproteins; b) examining the biogenesis of lipoprotein particles found to be unique to peripheral lymph; c) defining the metabolic fate of the unique, discoidal "interstitial" HDL particle; d) examining the production of apo A-IV-containing particles by the intestine and liver and their role in interstitial fluid; and e) studying the mechanism of the formation in the interstitial fluid of apo A-I unassociated with conventional lipoprotein particles. 2. To study in vivo modification of lipoproteins in the circulation by: a) examining the remodeling of "interstitial" lipoproteins and determining the processes involved; b) studying the dynamics of lipoprotein remodeling (particularly apo A-IV particles and apo A-I unassociated with lipoproteins) in plasma and peripheral lymph; c) examining how remodeling of plasma and lymph lipoproteins (their apolipoprotein and lipid components) influences their metabolism; and d) determining how this remodeling may be involved in reverse cholesterol transport. 3. To study apoprotein synthesis by : a) defining the biogenesis and molecular structure of apo B; b) determining the physiologic importance of apo B phosphorylation with regard to VLDL assembly/secretion; and c) determining the genetic expression of apo B caused by physiologic "effectors." We are also studying apolipoprotein synthesis by peripheral tissues, both in vivo in vitro. We believe these studies will contribute to our understanding of lipoprotein-apoprotein metabolism and its physiologic role in lipid homeostasis.