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GASTROINTESTINAL PROTEINS--CELL AND MOLECULAR REGULATION

胃肠道蛋白质——细胞和分子调节

基本信息

批准号：
2139072
负责人：
DAVID H. ALPERS
金额：
$ 105.69万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
1987
资助国家：
美国
起止时间：
1987-01-05 至 1995-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/2139072
关键词：
gastrointestinal epithelium gene expression

项目摘要

The overall goal of this program is to examine the function and biology of proteins in gastrointestinal tissues at the cellular and molecular level. Project will study several genes and their protein products expressed in cells of foregut origin (chief and parietal cells of stomach, salivary acini and ducts, pancreatic exocrine cells) (projects 1-3); in enterocytes (projects 4-6), or in hepatocytes (project 6). Gene products to be studied include cobalamin binding proteins (project 1), intrinsic factor (project 2), lipase and colipase (project 3), alpha 1- antitrypsin and antichymotrypsin (project 4), liver and intestinal fatty acid binding proteins (project 5), and long chain acyl CoA dehydrogenase (project 6). Different aspects of the same proteins will be studied in more than one project, reinforcing an integrated approach (intrinsic factor; projects 1, 2; L-FABP, projects 4, 5). Two major focuses are to study the regulation of gene expression in epithelial cells of the gastrointestinal tract, and to determine the relationship between structure and function of certain gastrointestinal proteins. Gene expression will be studied by analysis of transcriptional regulation (projects 2, 3, 4, 6) and in response to environmental factors, such as dietary or hormonal stimuli, during inflammatory response, or adaptation to intestinal reaction or bypass (projects 1, 3, 4, 5, 6). Structure/function studies will include cobalamin binding proteins (project 1), pancreatic lipase and colipase (project 3), and long chain acyl CoA dehydrogenase (project 6). Techniques from molecular biology (projects 1-6), and cell biology (projects 1, 2, 3, 4, 5) will be used. The Program project will utilize the original three core facilities (biomolecular analysis, morphology, and cell culture), including HPLC (for peptide separations), protein sequencers, oligodeoxynucleotide synthesizers, cell culture of intestinal and pancreatic cell lines, light and electron microscopy, computer assisted morphometric analyses, immune localization, and in situ hybridization. These studies will use model systems to provide insights into 1) synthesis and processing of cellular and secreted gastrointestinal proteins, 2) molecular mechanisms of cellular differentiation and adaptation, 3) relationship between structure and function of specific gut proteins, and 4) biochemical changes related to three human disorders, pancreatic insufficiency (project 3), short bowel syndrome (project 5), and long chain acyl CoA dehydrogenase deficiency (project 6).

该计划的总体目标是检查功能和生物学胃肠道组织中蛋白质的细胞和分子水平等级。项目将研究几种基因及其蛋白质产物在前肠来源的细胞（主细胞和壁细胞）中表达胃、唾液腺腺泡和导管、胰腺外分泌细胞）（项目 1-3);在肠细胞中（项目 4-6），或在肝细胞中（项目 6）。基因待研究的产品包括钴胺素结合蛋白（项目1），内因子（项目 2）、脂肪酶和辅脂肪酶（项目 3）、α 1- 抗胰蛋白酶和抗胰凝乳蛋白酶（项目4），肝脏和肠道脂肪酸结合蛋白（项目 5）和长链酰基 CoA 脱氢酶（项目 6）。将研究相同蛋白质的不同方面多个项目，加强综合方法（内在因素;项目1、2； L-FABP，项目 4、5)。两个主要重点是研究上皮细胞基因表达的调控胃肠道，并确定两者之间的关系某些胃肠道蛋白质的结构和功能。基因将通过转录调控分析来研究表达（项目 2、3、4、6）并响应环境因素，例如炎症反应或适应过程中的饮食或激素刺激肠道反应或绕道（项目 1、3、4、5、6）。结构/功能研究将包括钴胺素结合蛋白（项目 1）、胰脂肪酶和辅脂肪酶（项目 3）和长链酰基 CoA 脱氢酶（项目 6）。分子生物学技术（项目 1-6）和细胞生物学（项目 1、2、3、4、5）将被使用。该计划项目将利用原有的三大核心设施（生物分子分析、形态学和细胞培养），包括 HPLC （用于肽分离）、蛋白质测序仪、寡脱氧核苷酸合成器、肠道和胰腺细胞系的细胞培养，光学和电子显微镜、计算机辅助形态分析、免疫定位和原位杂交。这些研究将使用模型系统提供对 1) 合成和处理的见解细胞和分泌的胃肠蛋白，2) 分子机制细胞分化和适应的关系，3）特定肠道蛋白的结构和功能，4) 生化与三种人类疾病（胰腺功能不全）相关的变化（项目 3）、短肠综合征（项目 5）和长链酰基 CoA 脱氢酶缺乏症（项目 6）。