SALIVARY MUCIN SYNTHESIS, PROCESSING AND SECRETION

唾液粘蛋白是一类生物活性范围广泛的糖蛋白。 从保护膜的形成到特定菌株的聚集 口腔细菌。该项目的最终目标是提供一个 口腔疾病相关治疗的生物学基础 唾液中粘蛋白不足。这将基于 对导致产生和释放的机制的理解 唾液腺中的粘蛋白。在模型系统方面取得了进展。 小鼠，这是模仿正常的昼夜周期，其主要 优点是个体之间的同步性和较小的差异。这个 要应用于该模型系统的分析针对的是两种非蛋白粘蛋白 合成和糖基化，提供了检测来源的能力 粘蛋白本身或由唾液产生的功能障碍 腺体。该系统将被监控以控制无粘蛋白的合成。 在转录和转录后水平，这两者都有 是从其他研究中得出的结论。因为颌下和舌下 腺体在以下范围内提供了不同的分析优势 模型系统，两者的粘蛋白都包括在研究中，以及 已经为每种方法开发了量化方法。粘蛋白基因 序列特异性探针目前正在开发中。最新研究 对老鼠的研究表明，唾液粘蛋白水平随着年龄的增长而下降， 对人类来说，表明体内两种主要粘蛋白的浓度 唾液会随着年龄的增长而减少。我们现在将测试衰老是否也会导致 粘蛋白的“质”变化 小鼠唾液腺粘蛋白的碳水化合物分析。另一个 这个项目的重点是唾液腺现象 过度刺激及其在显性腺体病例中的可能应用 功能减退。在早期的研究中，我们观察到粘蛋白含量和 衰老小鼠颌下腺的浓度 通过重复用药刺激超过衰老前的水平 异丙肾上腺素。结果表明，这些升高的激素水平 腺体粘蛋白也会导致唾液中的粘蛋白水平升高。最初， 其他激动剂过度刺激粘蛋白堆积的潜力将是 评估，然后测试过度刺激的持久性 状态，以及可能的副作用。

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.