GASTROINTESTINAL PROTEINS CELL AND MOLECULE REGULATION

胃肠蛋白细胞和分子调节

• 批准号: 3095307
• 负责人: DAVID H. ALPERS
• 金额: $ 92.94万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-01-05 至 1991-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3095307
• 关键词: chemical structure function; gastrointestinal system; genetic regulation; in situ hybridization; lipid metabolism; proteins

The goal of this program is to examine the physiological responses of proteins in several gastrointestinal tissues at the cellular and molecular level under common environmental conditions (developmental, dietary, inflammatory, and metabolic or hormonal). Some projects will study proteins produced by cells of ectodermal origin (enterocyte, chief cells of stomach, pancreatic exocrine cells); some will study proteins secreted by inflammatory cells in the intestinal mucosa. Proteins to be studied include apolipoproteins (project 1), entercoyte brush border and basolateral membrane protein (project 2), maltase-glucoamylase (project 3), immunoglobulius (project 4), cobalamin binding proteins (project 5), and pancreatic lipase and colipase (project 6). The techniques used will be derived from molecular biology (projects 1,3,5), cell biology (projects 1,2,6), and immunology (projects 4,6). These studies require facilities which can be conveniently shared, and include HPLC (for peptide and lipid separations), protein sequenators, oligodeoxynucleotide synthesizer, cell culture of lymphocytes, intestinal (e.g. CaCo2) and hepatic (HepG2) cell lines, and light and electron microscopy for morphology, immune localization, and in situ hybridization. The project will allow the formation of three core facilities (biomolecular analysis, morphology, and cell culture) which will be dedicated to carrying out research on gastrointestinal physiology at the cellular and molecular levels. These studies will provide insight into 1) the mechanism of cellular responses of gastrointestinal tissues to environmental changes, 2) the molecular mechanisms of gut differentiation, 3) the synthesis and processing of cellular and secreted gastrointestinal proteins, and 4) the biochemical changes in three human disorders, sucrase- isomaltase deficiency (project 3), pernicious anemia (project 5), and pancreatic insufficiency (project 6).

这个项目的目标是检查生理反应 几种胃肠道组织中的蛋白质在细胞和 常见环境条件下的分子水平 (发育、饮食、炎症和代谢或 荷尔蒙)。一些项目将研究由人的细胞产生的蛋白质 外胚层起源(肠细胞、胃主要细胞、胰腺 外分泌细胞)；一些人将研究炎症分泌的蛋白质 肠粘膜中的细胞。待研究的蛋白质包括 载脂蛋白(项目1)，肠细胞刷状缘和 基侧膜蛋白(项目2)，麦芽糖酶-糖淀粉酶 (项目3)，免疫球蛋白(项目4)，钴胺结合 蛋白质(项目5)、胰腺脂肪酶和乳脂酶(项目6)。 所使用的技术将源自分子生物学。 (项目1、3、5)、细胞生物学(项目1、2、6)和免疫学 (项目4，6)。这些研究需要的设施可以 方便共享，包括高效液相色谱(用于肽和脂类 分离)、蛋白质测序仪、寡脱氧核苷酸 肠道淋巴细胞细胞培养合成器(如CaCO2) 和肝(HepG2)细胞系，以及光镜和电子显微镜 用于形态、免疫定位和原位杂交。 该项目将形成三个核心设施 (生物分子分析、形态和细胞培养) 致力于开展胃肠生理学研究 在细胞和分子水平上。这些研究将提供 洞察1)细胞反应的机制 胃肠道组织对环境变化的反应，2) 肠道分化的分子机制，3)合成和 细胞和分泌的胃肠道蛋白的加工，以及 4)三种人类疾病的生化变化，蔗糖酶- 异麦芽糖酶缺乏症(项目3)、恶性贫血(项目5)、 和胰腺功能不全(方案6)。