APOLIPOPROTEIN METABOLISM: REGULATION AND FUNCTION

该方案项目的中心主题是监管 载脂蛋白代谢及其在脂质和 脂蛋白稳态 为了实现这一目标，我们组织了一个 涉及生理学，生物化学， 免疫化学和细胞生物学，采用在体内和在 体外技术 我们建议以下广泛领域： 调查： 1. 研究外周淋巴脂蛋白代谢：a） “间质”脂蛋白的进一步表征; B） 检查脂蛋白颗粒的生物发生， 外周淋巴特有的; c）定义外周淋巴细胞的代谢命运， 独特的盘状“间质”HDL颗粒; d）检查 通过肠产生含apo A-IV的颗粒， 肝脏及其在间质液中的作用;以及e）研究 载脂蛋白A-I在组织液中的形成机制 与常规脂蛋白颗粒无关。 2. 研究脂蛋白在体内的修饰， 循环方式：a）检查“间质”重塑 脂蛋白并确定所涉及的过程; B）研究 脂蛋白重塑的动力学（特别是载脂蛋白A-IV 颗粒和载脂蛋白A-I与脂蛋白无关）， 外周淋巴; c）检查血浆和淋巴的重塑如何 脂蛋白（其载脂蛋白和脂质成分）影响 他们的新陈代谢;和d）确定这种重塑如何可能是 参与胆固醇的逆向运输 3. 研究载脂蛋白的合成：a）确定生物起源 和载脂蛋白B的分子结构; B）测定载脂蛋白B的生理活性， 载脂蛋白B磷酸化对极低密度脂蛋白重要性 组装/分泌;以及c）确定以下的基因表达： apo B由生理“效应物”引起。“我们也在研究 载脂蛋白的合成，无论是在体内， 体外 我们相信这些研究将有助于我们了解 脂蛋白-载脂蛋白代谢及其在脂质中的生理作用 体内平衡

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.