salivary proteins l.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
Salivary Proteins PowerPoint Presentation
Download Presentation
Salivary Proteins

Loading in 2 Seconds...

play fullscreen
1 / 18

Salivary Proteins - PowerPoint PPT Presentation


  • 210 Views
  • Uploaded on

Salivary Proteins. DENT 5302 Topics in Dental Biochemistry Dr. Joel Rudney. Supplemental reading. Rudney JD (2000). Saliva and Dental Plaque. Adv Dent Res 14:29-39. Lamkin MS, Oppenheim FG (1993). Structural features of salivary function. Crit Rev Oral Biol Med 4:251-259.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

Salivary Proteins


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
salivary proteins

Salivary Proteins

DENT 5302

Topics in Dental Biochemistry

Dr. Joel Rudney

supplemental reading
Supplemental reading

Rudney JD (2000). Saliva and Dental Plaque. Adv Dent Res 14:29-39.

Lamkin MS, Oppenheim FG (1993). Structural features of salivary function. Crit Rev Oral Biol Med 4:251-259.

clinical importance
Clinical Importance
  • Demographic change - the number of elderly will increase
  • Implications:
    • Increases in diseases affecting salivary glands
      • Sjogren's syndrome, other autoimmune diseases,
      • Head and neck cancer (radiation therapy)
    • Increased use of medications with effects on saliva
      • Anticholinergic (antihistamines, antidepressants)
        • Reduced flow - indirect/direct effects on proteins
      • Beta adrenergic agonists and antagonists
        • Direct effects on protein synthesis/secretion
        • (asthma, hypertension, cardiovascular disease)
salivary protein therapies
Salivary protein therapies
  • Current artificial salivas replace mainly fluids, ions
  • Genetically-engineered human salivary proteins soon
    • Raised from seed
    • Which ones go in artificial saliva? How much to add?
  • Already toothpastes/rinses containing saliva proteins
    • Biotène™ (peroxidase, lysozyme lactoferrin)
    • Histatin rinses/gels in trials
  • Clinicians will need to be able to evaluate new products
origins of salivary proteins
Origins of salivary proteins
  • Different secretory cells in different glands
    • Serous acinar - water, ions, proteins
      • Most in parotid, less in SM/SL
    • Mucus acinar - complex glycoproteins
      • Only SM/SL and minor glands
    • Different proteins emphasized in different glands
    • Duct cells also secrete proteins - differs among glands
  • Immune system cells contribute proteins
    • B cell product (S-IgA) translocated into ducts
    • Neutrophils - indirect leakage into gingival crevice
  • Leakage from gingival fluid contributes serum proteins (WS only)
  • Oral epithelial cells release surface proteins (whole saliva only)
functions protect tissues
Functions - Protect tissues
  • Protect oral surfaces by forming pellicle
    • Statherin, acidic proline-rich proteins, amylase, histatins, cystatins, MUC7 mucin, lysozyme, albumin, carbonic anhydrase
  • Lubrication - oral surfaces must slide freely
    • Statherin, MUC5B mucin (also reflux protection)
  • Maintain saliva calcium in equilibrium with enamel
    • Saliva supersaturated with calcium and phosphate
    • Precipitation must be prevented
    • Statherin, aPRP, histatins, cystatins
functions food processing
Functions - Food processing
  • Initial breakdown of starches - Amylase
  • Binding/detoxification of dietary tannins
    • aPRP, basic PRP, histatins
  • Protein processing - Kallikrein and other proteases
  • Swallowing - MUC5B
functions manage microbes
Functions - Manage Microbes
  • Antimicrobial functions (bacteria, fungi, viruses)
    • Direct - cell killing - Histatins, lysozyme, amylase, MUC7, lactoferrin, defensins, peroxidase
    • Indirect - Inhibition of infectivity, microbial metabolism, bacterial/viral proteases - Lactoferrin, cystatins, histatins,basic PRP, SLIPI, peroxidase, S-IgA
    • "Aggregation" - bind to microbes, clear by swallowing - MUC7,lysozyme, lactoferrin, glcosylated PRP, parotid agglutinin, extra-parotid glycoprotein, S-IgA
functions microbes manage
Functions - Microbes Manage
  • Microbial use of saliva proteins (coevolution)
    • Microbial adherence to pellicle proteins - Statherin, aPRP, amylase, MUC5B, MUC7,lysozyme, lactoferrin, glcosylated PRP, parotid agglutinin, extra-parotid glycoprotein, S-IgA, peroxidase
    • Microbial metabolism of salivary proteins - MUC5B
    • Microbial use to metabolize host diet - Amylase
complexity and redundancy
Complexity and Redundancy
  • Most saliva proteins have more than one function
    • Different domains on the same protein for different functions
  • Most saliva proteins cans be "amphifunctional”
    • Some actions help host, others seem to help microbes
    • Also can be mediated by different domains
  • Many proteins share similar functions - redundancy
    • Multiple gene families
      • 2-4 closely linked genes coding very similar proteins
        • aPRP, bPRP, gPRP, cystatins, histatins ,amylase, MUCs
        • Multiple alleles for each gene
    • Unrelated proteins with the same function - backup systems?
fragments and complexes
Fragments and Complexes
  • Many salivary proteins are cleaved by proteases
    • During secretion or in the mouth
      • aPRP, bPRP, gPRP, histatins,S-IgA
    • Fragments may function differently than intact proteins
  • Proteins function differently together than they do alone
    • Lysozyme, lactoferrin, peroxidase
  • Salivary proteins bind in large heterotypic complexes
    • MUC5B, amylase, aPRP, S-IgA, peroxidase, lysozyme, lactoferrin, statherin
    • Complexes function differently than component proteins
pictures of proteins in pellicle
Pictures of proteins in pellicle

aPRP

statherin

histatins

Schupbach et. al. 2001, Eur J Oral Sci 109:60

pictures of proteins in pellicle13
Pictures of proteins in pellicle

statherin

histatins

Schupbach et. al. 2001, Eur J Oral Sci 109:60

statherin up close
Statherin up close
  • Multiple gene family
  • Small tyrosine-rich phosphoproteins
  • Negatively charged Ca2+ binding N-terminal
    • Two phosphoserines - additional negative charges
    • Maintains Ca2+ balance, strongly prevents precipitation
  • Binds tooth surfaces and changes conformation
    • C-terminal rich in "bulky" tyrosines
    • Lubrication of tooth surfaces (pellicle)
    • Adherence of Actinomyces species (pellicle)
acidic prp up close
Acidic PRP up close
  • Multiple gene family
  • Proline-rich phosphoproteins
    • Negatively charged Ca2+ binding N-terminal
    • Two phosphoserines - additional negative charges
    • Ca2+ balance, strongly prevents precipitation
  • Binds tooth surfaces and changes conformation
    • C-terminal rich in "bulky" prolines
    • Adherence of Streptococcus species (pellicle)
  • Proteases cleave N-terminal from C-terminal
    • Free C-terminal binds tannins; blocks bacterial adhesion
histatins up close
Histatins up close
  • Multigene family - largest is phosphoprotein, others not
  • Small peptides after proteolysis
    • Positive charge - histidine-rich
  • Microbial cell damage - antibacterial and anti-fungal
    • Also Ca2+ balance, tannin binding, protease inhibitor
  • Clinical interest - very safe - easy to make
    • Early trials with histatin rinses and gels
      • Some benefit in experimental gingivitis model
        • No oral hygiene for a month
    • No trials with caries, periodontitis, or candidiasis patients yet
current products
Current Products
  • Products with added lysozyme, lactoferrin, peroxidase
  • All influence aggregation/adherence, plus unique effects
    • Px enzyme - bacterial H2O2 + saliva SCN- > OSCN-
      • OSCN- inhibits/kills bacteria
      • Removing H2O2 may protect soft tissues
    • Lz enzyme cleaves bacterial cell walls > lysis
      • Also positive charge effects similar to histatins
    • Lf sequesters iron from some microbes, but not all
      • Unsaturated Lf is independently bactericidal
  • Clinical interest - can be purified from cow's milk
    • Biotène™ toothpaste, rinses, gum, dry mouth gels
      • Minor to minimal benefit in published clinical trials
future prospects
Future Prospects
  • Ideas about salivary protein function come from lab
  • Experimental models are greatly simplified
    • Change only one factor at a time
  • The mouth is an extremely complex environment
    • Difficult to isolate effects of single proteins
    • Redundancy may “dilute” the effects of supplements
  • We need to understand how different proteins work together
    • Supplements may need to be in the form of protein complexes