MOLECULAR MECHANISMS OF APOLIPOPROTEIN B BIOGENESIS

描述：（改编自研究者摘要）： 研究者提出研究载脂蛋白B（apo B）生物发生 和含载脂蛋白B的脂蛋白颗粒形成。 载脂蛋白B主要 在胆固醇运输中的作用 高胆固醇血症是一个危险因素， 动脉粥样硬化和冠状动脉疾病。 一些患者的血压升高 血清胆固醇在载脂蛋白B结构中具有已知缺陷。 许多其他人所 含有脂蛋白的载脂蛋白B代谢中的未表征的畸变， 这可能与有缺陷的组装有关。 了解这些 多种病变引起高脂蛋白血症需要详细的知识 正常脂蛋白颗粒组装的机制， 秘密的 然而，脂蛋白颗粒组装的重要特征是 人们对蛋白质的了解很少，也不容易用蛋白质的当前价值来解释 生物起源和贩运。 最近，调查人员发现 在载脂蛋白B易位的早期事件中， 内质网膜（见初步研究）的表达， 在两种膜补充的细胞中克隆编码apo B结构域的cDNA， 无细胞系统和活细胞中。 这些中间体将 表征并与载脂蛋白B的阶段相关 颗粒组装、调节和分泌。 该分析将 延伸到载脂蛋白B生物发生的后期事件。 通过这些实验，A 更好地了解载脂蛋白B的生物发生及其与 将出现脂蛋白颗粒形成。 新的洞察 apo B可能在以下条件下进行事后调节的机制 生理条件和高胆固醇血症脂蛋白疾病 人类可以跟随。

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.