REGULATION OF DERMATAN SULFATE FORMATION BY CHONDROCYTES

软骨细胞对硫酸皮肤素形成的调节

• 批准号: 2882735
• 负责人: ROBERT KOKENYESI
• 金额: $ 0.44万
• 依托单位: STATE UNIVERSITY OF NEW YORK AT BUFFALO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-03-01 至 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882735
• 关键词: CD8 molecule; Golgi apparatus; SDS polyacrylamide gel electrophoresis; affinity chromatography; autoradiography; carbohydrate biosynthesis; chimeric proteins; chondrocytes; chondroitin sulfate B; chondroitin sulfates; crosslink; decorin; glycoprotein biosynthesis; intermolecular interaction; mucopolysaccharides; protein binding; protein structure function; proteoglycan; stereochemistry; tissue /cell culture

DESCRIPTION: This project addresses the biochemical mechanism which regulates proteoglycan chain specific glycosaminoglycan modification. Three proteoglycan and their core proteins will be studied (aggrecan, biglycan and decorin) using an immortalized clonal mouse chondrocyte cell line that reproduces the core-specific epimerization observed in cartilage in vivo. The distinctive functions of dermatan sulfate proteoglycans in regulation of collagen fibrillogenesis, compared with that for space filling and water retaining form such as aggrecan, justify efforts here to understand the process controlling their biosynthesis. These studies arise from the hypothesis that both the initiation and extent of epimerization is regulated by selective protein-protein interactions of proteoglycan core proteins with intra-Golgi proteins during glycosaminoglycan biosynthesis. The specific aims are : 1) to use intra Golgi cross-linking and affinity chromatography on core protein-derivatized support to determine whether core proteins of aggrecan, decorin, and biglycan interact with specific sets of intra-Golgi proteins; and 2) to assess the feasibility for an innovative approach to characterize the microenvironment of core proteins within the Golgi apparatus by the immunoisolation of Golgi-derived vesicles that contain aggrecan, decorin, or biglycan. These studies are expected to enhance understanding of epimerization of dermatan sulfate which may impact other research areas through characterization of a novel regulatory mechanism in proteoglycan biosynthesis and of novel processes in Golgi trafficking and sorting.

描述：该项目解决了生化机制 调节蛋白聚糖链特异性糖胺聚糖的修饰。 三 将研究蛋白聚糖及其核心蛋白质（Aggrecan，Biglycan和 Decorin）使用永生的克隆小鼠软骨细胞细胞系 再现体内软骨中观察到的核心特异性表达化。 皮肤硫酸盐蛋白聚糖在调节中的独特功能 与空间填充和水相比，胶原蛋白原纤维生成 保留诸如Aggrecan之类的形式，在这里为了解 控制其生物合成的过程。 这些研究来自 假设表达的起始和程度都受到调节 通过选择性蛋白质 - 蛋白质蛋白的相互作用，蛋白聚糖核心蛋白与 糖胺聚糖生物合成期间高尔基体内蛋白。 具体 目的是：1）使用高尔基体交联和亲和力色谱法 在核心蛋白衍生的支持上，以确定是否核心蛋白 Aggrecan，Decorin和Biglycan与特定的Golgi相互作用 蛋白质； 2）评估创新方法的可行性 表征高尔基体内核心蛋白的微环境 通过含有高尔基衍生囊泡的免疫分散的设备 Aggrecan，Decorin或Biglycan。 这些研究有望增强 了解可能影响其他的硫酸真皮硫酸盐的含量 通过表征新的调节机制的研究领域 蛋白聚糖的生物合成和高尔基贩运和新过程 排序。