A key purpose of this proposal is to standardize and describe in vivo the stimulus-secretion-synthesis cycle of a mouse submandibular gland mucin. This system is intended to provide insight into the control and synthesis processes which are responsible for the diurnal replenishment of exocrine proteins in the salivary glands. It is postulated that by clarifying the normal flow of events, it will be possible to begin to understand some forms of salivary gland dysfunction. Protocols are described for obtaining rates of synthesis and degradation of the mucin core protein at different stages of the cycle. Rates and sequence of mucin oligosaccharide assembly will also be ascertained. A strategy for identifying the mechanism for activation of the synthesis phase is described and possible coordination between translation and glycosylation processes will be tested. The final phase of this part of the project will be to examine the effects of different stimuli on the cycle. We will extend to senescent mice our recent study with young to mid-adult mice which indicated that mucin oligosaccharide composition was stabilized by chronic isoproterenol treatment. The intent of this phase of the study is to determine if the carbohydrate composition of mucin varies more in old mice than in young and if isoproterenol treatment can reduce this variation. The effects of chronic pilocarpine treatment will be tested in the same age groups. A study of the relationship of different secretagogues to mucin concentrations in saliva will be repeated and extended in a mouse population in which inherent variation has been reduced substantially. Steps have been taken to provide this population and additional approaches are under investigation. In the previous study, a greater than 60-fold range of mucin concentrations in saliva was observed following stimulation of secretion with the same dosage of pilocarpine in different animals of a regular laboratory population. We plan to compare effects of different dosages but do not predict success unless the inherent variation is reduced. Finally, we present evidence suggesting that mucin undergoes an oligosaccharide processing step at secretion. Two protocols will test this possibility. If processing is confirmed, we will determine which class of oligosaccharides is affected, how this impacts intracellular sialic acid and the mechanisms involved.

Agency
National Institute of Health (NIH)
Institute
National Institute of Dental & Craniofacial Research (NIDCR)
Type
Research Project (R01)
Project #
5R01DE006892-07
Application #
3220381
Study Section
Oral Biology and Medicine Subcommittee 1 (OBM)
Project Start
1984-03-01
Project End
1992-02-29
Budget Start
1990-03-01
Budget End
1991-02-28
Support Year
7
Fiscal Year
1990
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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