SALIVARY MUCIN SYNTHESIS, PROCESSING AND SECRETION

唾液粘蛋白​​的合成、加工和分泌

• 批准号: 2129408
• 负责人: PAUL C DENNY
• 金额: $ 20.21万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-08-01 至 1996-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2129408
• 关键词: RNA biosynthesis; aging; antiserum; carbachol; glycoprotein biosynthesis; glycosylation; human subject; isoproterenol; laboratory mouse; laboratory rabbit; laboratory rat; messenger RNA; molecular cloning; mucins; nucleic acid probes; nucleic acid sequence; oligosaccharides; pilocarpine; polysomes; posttranslational modifications; ribonucleoproteins; saliva; salivary glands; secretion; sublingual gland; submandibular gland; western blottings

Mucins from saliva are a class of glycoproteins whose bioactivities range from formation of protective coatings to aggregation of specific strains of oral bacteria. The ultimate goal of this project is to provide a biological rationale for treatments of oral conditions related to insufficiency of mucin in saliva. This would be based on an understanding of the mechanisms leading to production and release of mucins from salivary glands. Progress has been made on a model system in mice, which is patterned after the normal diurnal cycle, whose main advantages are synchrony and reduced variation between individuals. The analyses to be applied to this model system are directed to both apomucin synthesis and glycosylation, providing the ability to detect the source of dysfunction either in mucin itself or in its production by salivary glands. The system will be monitored for control of apomucin synthesis at transcriptional and post-transcriptional levels, both of which have been implied from other studies. Since submandibular and sublingual glands provide different advantages for analysis within the confines of the model system, the mucins of both are included in the study, and quantitation methods have been developed for each. Mucin gene sequence-specific probes are currently under development. Recent studies with mice indicate that salivary mucins levels decline with aging and, with humans, suggest that the concentrations of both major mucins in saliva are reduced with aging. We will now test if aging also leads to "qualitative" changes in mucin using a protocol developed for carbohydrate analysis of mucin from a mouse salivary gland. Another aspect of this project focuses on the phenomenon of salivary gland hyperstimulation and its possible application to cases of apparent gland hypofunction. In earlier studies, we observed that mucin content and concentration of submandibular glands of senescent mice could be stimulated to exceed pre-senescent levels by repeated treatments with isoproterenol. It was subsequently shown that these elevated levels of gland mucin also led to elevated levels in the saliva. Initially the potential of other agonists to hyperstimulate mucin accumulation will be evaluated, followed by tests for persistence of the hyperstimulated state, and of possible side-effects.

唾液粘蛋白是一类糖蛋白，其生物活性范围 从形成保护膜到特定菌株的聚集 口腔细菌。 该项目的最终目标是提供一个 治疗口腔疾病的生物学原理 唾液中粘蛋白不足。 这将基于一个 了解导致生产和释放的机制， 唾液腺粘蛋白。 年在一个模型系统方面取得了进展， 小鼠，这是正常的昼夜周期后，其主要模式 优点是个体之间的同步和减少的变化。 的 应用于该模型系统的分析涉及脱粘蛋白和脱粘蛋白 合成和糖基化，提供检测来源的能力 粘液本身或唾液分泌的粘液产生功能障碍 腺体 将监测系统以控制脱粘蛋白合成 在转录和转录后水平，两者都有 从其他研究中得到了启示。 因为下颌下和舌下 腺体提供了不同的优势，分析范围内， 模型系统，两者的粘蛋白都包括在研究中，并且 已经为每一种开发了定量方法。 粘蛋白基因 目前正在开发序列特异性探针。 最近的研究 表明唾液粘蛋白水平随着年龄的增长而下降， 与人类，这表明，两个主要粘蛋白的浓度， 唾液随着年龄的增长而减少。 我们现在将测试老化是否也会导致 粘蛋白的“定性”变化， 小鼠唾液腺粘蛋白的碳水化合物分析。 另一 这个项目的一个方面集中在唾液腺的现象 过度刺激及其在表观腺体病例中应用的可能性 机能减退 在早期的研究中，我们观察到粘蛋白含量和 衰老小鼠下颌下腺的浓度可以 通过重复处理刺激超过衰老前水平， 异丙肾上腺素 随后的研究表明，这些高水平的 腺粘蛋白也导致唾液中的水平升高。 最初 其他激动剂过度刺激粘蛋白积累的潜力将是 评估，然后进行测试的持久性的过度刺激 以及可能的副作用。