SALIVARY MUCIN SYNTHESIS, PROCESSING AND SECRETION

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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.