MOLECULAR MECHANISMS OF APOLIPOPROTEIN B BIOGENESIS

描述：(改编自调查人员摘要)： 研究人员建议研究载脂蛋白B(Apo B)的生物发生 含载脂蛋白B的脂蛋白颗粒形成。载脂蛋白B是一个主要的 在胆固醇运输中的作用。高胆固醇血症是高血压的危险因素 动脉粥样硬化和冠状动脉疾病。一些患者的心脏抬高 血清胆固醇在载脂蛋白B结构中有一个已知的缺陷。其他许多人都有 含脂蛋白的载脂蛋白代谢的不明异常， 这可能与有缺陷的组件有关。对这些问题的理解 引起高脂蛋白血症的不同病变需要详细的知识 正常脂蛋白颗粒的组装机制和 秘而不宣。然而，脂蛋白颗粒组装的重要特征是 很难理解，也不容易用蛋白质的现值解释 生物发生和贩运。最近，调查人员发现 载脂蛋白B易位早期事件中的不寻常中间产物 内质网膜(见初步研究)的表达 两种膜补充剂中载脂蛋白B结构域编码基因的克隆 无细胞系统和活细胞中。这些中间体将是 载脂蛋白B的特征及其与分期的关系 颗粒的组装、调节和分泌。这一分析将是 延伸到载脂蛋白B生物发生的后期事件。通过这些实验， 更好地理解载脂蛋白B的生物发生及其与 会出现脂蛋白颗粒的形成。新的洞察力 载脂蛋白B的翻译后调控机制 生理条件与高胆固醇血症脂蛋白紊乱 人类可能会效仿。

DESCRIPTION: (Adapted from the Investigator's abstract): The investigators propose to investigate apolipoprotein B (apo B) biogenesis and apo B-containing lipoprotein particle formation. Apo B plays a major role in cholesterol transport. Hypercholesterolemia is a risk factor for atherosclerosis and coronary artery disease. Some patients with elevated serum cholesterol have a known defect in apo B structure. Many others have uncharacterized aberrations in metabolism of apo B containing lipoproteins, which may be related to defective assembly. An understanding of how these diverse lesions cause hyperlipoproteinemia will require detailed knowledge of the mechanism by which a normal lipoprotein particle is assembled and secreted. Yet, important features of lipoprotein particle assembly are poorly understood and not easily explained by current value of protein biogenesis and trafficking. Recently, the investigators have discovered unusual intermediates in the early events of apo B translocation across the endoplasmic reticulum membrane (see Preliminary Studies) by expression of cloned cDNAs encoding domains of apo B in both membrane-supplemented cell-free systems and in living cells. These intermediates will be characterized and related to stages in apo B-containing lipoprotein particle assembly, regulation and secretion. This analysis will be extended to later events in apo B biogenesis. Through these experiments a better understanding of apo B biogenesis and its relationship to lipoprotein particle formation will emerge. New insight into the mechanisms by which apo B may be post-translationally regulated under physiologic conditions and in hypercholesterolemic lipoprotein disorders of humans may follow.