STRUCTURE AND FUNCTION OF INTESTINAL MUCIN

肠粘蛋白的结构和功能

• 批准号: 3228659
• 负责人: JOHN THOMAS LAMONT
• 金额: $ 16.17万
• 依托单位: BOSTON UNIVERSITY MEDICAL CENTER HOSP
• 依托单位国家: 美国
• 财政年份: 1980
• 资助国家: 美国
• 起止时间: 1980-07-01 至 1989-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3228659
• 关键词: acetylcysteine; bile; biliary tract disorder chemotherapy; bilirubin; calcium; cell membrane; chemical structure function; cholelithiasis; cholesterol; crystallization; detergents; disulfide bond; ethylenediaminetetraacetate; expectorant /mucolytic; gallbladder; gel; gel electrophoresis; human subject; hydropathy; ion exchange chromatography; light scattering; maleimides; mucins; organ culture; polymerization; radiotracer; reduction; solubility; thiols; tritium; viscosity

The long-term objectives of this proposal are to characterize the structure and properties of gallbladder mucin in experimental animals and man, and to elucidate the contribution of this glycoprotein to the pathophysiology of cholesterol and pigment gallstones. To accomplish these objectives we will employ biochemical and biophysical techniques to further define the structure of mucin, and will study nucleation and stone formation in vitro and in vivo. Our specific aims are as follows: 1. To determine the subunit structure of gallbladder mucin, particularly the contribution of disulfide bridges and hydrophobic interactions to polymer formation and gelation. Viscometric and quasielastic light scattering spectroscopy will be used to study gel formation of native mucin in solution. 2. To compare the ability of native and modified mucins from animals and human gallbladders to nucleate cholesterol monohydrate in bile. These studies will help to elucidate one mechanism of gallstone nucleation. 3. To test the ability of mucolytic agents to enhance gallstone dissolution in cholesterol solvents such as mono-octanoin and bile salts. These agents will be tested in vitro first, then in vivo on human gallstones implanted in gallbladders of experimental animals receiving a lithogenic diet. We also will study the formation and composition of biliary sludge in experimental animals and man, as this material, a precipitate of bilirubin and mucin, is thought to be a precursor of gallstones. These studies have direct relevance to human gallstone disease, and may lead to improved stone dissolution therapy.

本提案的长期目标是确定 和性质的胆囊粘蛋白在实验动物和人， 阐明这种糖蛋白的病理生理学的贡献， 胆固醇和胆色素结石。 为了实现这些目标，我们将 采用生物化学和生物物理技术，以进一步确定 粘蛋白的结构，并将在体外研究成核和结石形成 和体内。 我们的具体目标如下：1. 确定 胆囊粘蛋白的亚基结构，特别是 二硫桥和疏水相互作用形成聚合物， 凝胶化 粘度和准弹性光散射光谱将 用于研究溶液中天然粘蛋白的凝胶形成。 2.比较 来自动物和人天然和修饰的粘蛋白 胆囊使胆汁中的胆固醇一水合物成核。 这些研究 将有助于阐明胆结石成核的一种机制。 3.测试 粘液溶解剂增强胆结石溶解的能力 胆固醇溶剂如单辛酸甘油酯和胆汁盐。 这些试剂 将首先在体外进行测试，然后在体内植入人体胆结石 在接受致石饮食的实验动物的胆囊中。 我们 还将研究胆汁污泥的形成和组成， 实验动物和人，作为这种材料，胆红素沉淀 和粘蛋白，被认为是胆结石的前兆。 这些研究 直接关系到人类胆结石疾病，并可能导致改善结石 溶解疗法