APOLIPOPROTEIN METABOLISM: REGULATION AND FUNCTION

这一方案项目的中心主题是对 载脂蛋白代谢及其在脂质和脂肪代谢中的生理作用 脂蛋白动态平衡。为了实现这一目标，我们组织了一次 多学科方法，涉及生理学、生化、 免疫化学和细胞生物学，利用体内和体内 体外技术。我们提出了以下几个主要领域 调查： 1.研究外周淋巴脂蛋白代谢：a) “间质”脂蛋白的进一步特征；b) 研究发现脂蛋白颗粒的生物发生 外周淋巴所特有的；c)定义 独特的盘状“间隙”高密度脂蛋白颗粒；d)检查 含载脂蛋白A-IV的颗粒由肠道和 肝脏及其在间质液体中的作用；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.研究大鼠脂蛋白的体内修饰 循环方式：a)检查“间质”的重构 脂蛋白及其相关过程的测定；b)研究 脂蛋白重塑的动力学(尤其是载脂蛋白A-IV 与脂蛋白无关的颗粒和载脂蛋白A-I) 外周淋巴；c)检查血浆和淋巴的重塑 脂蛋白(其载脂蛋白和脂成分)的影响 他们的新陈代谢；以及d)确定这种重塑可能是如何 参与胆固醇的反向运输。 3.研究载脂蛋白的合成：a)定义生物发生 和载脂蛋白B的分子结构；b)决定生理 载脂蛋白B磷酸化对极低密度脂蛋白的重要性 组装/分泌；以及c)确定基因表达 载脂蛋白B是由生理“效应器”引起的。我们也在研究 外周组织中载脂蛋白的合成 体外培养。 我们相信这些研究将有助于我们理解 脂蛋白-载脂蛋白代谢及其在脂质中的生理作用 动态平衡。

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.