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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE006892-10
Application #
3220383
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1992-08-01
Project End
1995-07-31
Budget Start
1993-08-01
Budget End
1994-07-31
Support Year
10
Fiscal Year
1993
Total Cost
Indirect Cost
Name
University of Southern California
Department
Type
Schools of Dentistry
DUNS #
041544081
City
Los Angeles
State
CA
Country
United States
Zip Code
90089
Baughan, L W; Robertello, F J; Sarrett, D C et al. (2000) Salivary mucin as related to oral Streptococcus mutans in elderly people. Oral Microbiol Immunol 15:4-Oct
Liu, P; Denny, P A; Denny, P (2000) The effect of ageing on parenchymal cell populations in adult female mouse submandibular gland. Arch Oral Biol 45:585-92
Denny, P C; Liu, P; Denny, P A (1999) Evidence of a phenotypically determined ductal cell lineage in mouse salivary glands. Anat Rec 256:84-90
Nowroozi, N; Denny, P A; Denny, P C et al. (1998) Two gene products for beta-galactosidase are differentially expressed in the mouse salivary glands. J Craniofac Genet Dev Biol 18:51-7
Denny, P C; Ball, W D; Redman, R S (1997) Salivary glands: a paradigm for diversity of gland development. Crit Rev Oral Biol Med 8:51-75
Denny, P C; Mirels, L; Denny, P A (1996) Mouse submandibular gland salivary apomucin contains repeated N-glycosylation sites. Glycobiology 6:43-50
Denny, P C; Denny, P A; Hong-Le, N H (1995) Characterization of asparagine-linked oligosaccharides on a mouse submandibular mucin. Glycobiology 5:589-97
Bekhor, I; Wen, Y; Shi, S et al. (1994) cDNA cloning, sequencing and in situ localization of a transcript specific to both sublingual demilune cells and parotid intercalated duct cells in mouse salivary glands. Arch Oral Biol 39:1011-22
Navazesh, M; Mulligan, R A; Kipnis, V et al. (1992) Comparison of whole saliva flow rates and mucin concentrations in healthy Caucasian young and aged adults. J Dent Res 71:1275-8
Denny, P A; Hong, S H; Klauser, D K et al. (1992) Increased mucin levels in submandibular saliva from mice following repeated isoproterenol treatment. Arch Oral Biol 37:73-5

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