Salivary Proteins as a Defense Against Dietary Tannins

Abstract

Tannins, a diverse group of water-soluble phenolics with high affinity to proteins, are widely distributed in various parts of plants, and have negative effects in herbivores after ingestion. Some mammalian species are thought to counteract tannins by secreting tannin-binding salivary proteins (TBSPs). Several types of TBSPs are found in the saliva of laboratory animals, livestock, and wildlife. Among them, proline-rich proteins (PRPs) and histatins are effective precipitators of tannins. It is widely accepted that, at the least, PRPs act as a first line of defense against tannins. Many observations support this idea: in vitro affinity of PRPs to tannins is far higher than that of other proteins such as bovine serum albumin; complexes formed between PRPs and tannins are stable even under the conditions in the stomach and intestine; and PRP production is induced by ingesting tannins. It is believed that species that usually ingest tannins as part of their natural diets produce high levels of PRPs, whereas species not exposed to tannins produce little or no PRPs. This hypothesis is generally supported, although studies on TBSPs in wildlife are limited. This work stresses the importance of gathering basic information on such items as the characteristics of unidentified TBSPs, and seasonal and geographical variations in PRP production.

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References

  1. Ann, D. K. and Carlson, D. M. 1985. The structure of organization of a proline-rich protein gene of a mouse multigene family. J. Biol. Chem. 260:15863–15872.

    PubMed  CAS  Google Scholar 

  2. Ann, D. K., Gadbois, D., and Carlson, D. M. 1987. Structure, organization, and regulation of a hamster proline-rich protein gene—a multigene family. J. Biol. Chem. 262:3958–3963.

    PubMed  CAS  Google Scholar 

  3. Asquith, T. N. and Butler, L. G. 1985. Use of dye-labeled protein as spectrophotometric assay for protein precipitants such as tannin. J. Chem. Ecol. 11:1535–1544.

    Article  CAS  Google Scholar 

  4. Asquith, T., Mehansho, H., Rogler, J., Butler, L., and Carlson, D. M. 1985. Induction of proline-rich protein-biosynthesis in salivary-glands by tannins. FASEB J. 44:1097.

    Google Scholar 

  5. Asquith, T. N., Uhlig, J., Mehansho, H., Putman, L., Carlson, D. M., and Butler, L. 1987. Binding of condensed tannins to salivary proline-rich glycoproteins—the role of carbohydrate. J. Agric. Food. Chem. 35:331–334.

    Article  CAS  Google Scholar 

  6. Austin, P. J., Suchar, L. A., Robbins, C. T., and Hagerman, A. E. 1989. Tannin-binding proteins in saliva of deer and their absence in saliva of sheep and cattle. J. Chem. Ecol. 15:1335–1347.

    Article  CAS  Google Scholar 

  7. Azen, E. A., Carlson, D. M., Clements, S., Lalley, P. A., and Vanin, E. 1984. Salivary proline-rich protein genes on chromosomes-8 of mouse. Science 226:967–969.

    PubMed  Article  CAS  Google Scholar 

  8. Bacon, J. R. and Rhodes, M. J. C. 2000. Binding affinity of hydrolyzable tannins to parotid saliva and to proline-rich proteins derived from it. J. Agric. Food. Chem. 48:838–843.

    Article  PubMed  CAS  Google Scholar 

  9. Bennick, A. 2002. Interaction of plant polyphenols with salivary proteins. Crit. Rev. Oral Biol. Med. 13:184–196.

    PubMed  Article  Google Scholar 

  10. Bernays, E. A., Driver, G. C., and Bilgener, M. 1989. Herbivores and plant tannins. Adv. Ecol. Res. 19:263–302.

    Article  Google Scholar 

  11. Blytt, H. J., Guscar, T. K., and Butler, L. G. 1988. Antinutritional effects and ecological significance of dietary condensed tannins may not be due to binding and inhibiting digestive enzymes. J. Chem. Ecol. 14:1455–1465.

    Article  CAS  Google Scholar 

  12. Burritt, E. A. and Provenza, F. D. 2000. Role of toxins in intake of varied diets by sheep. J. Chem. Ecol. 26:1991–2005.

    Article  CAS  Google Scholar 

  13. Carlson, D. M. 1993. Salivary proline-rich proteins—biochemistry, molecular biology, and regulation of expression. Crit. Rev. Oral Biol. Med. 4:495–502.

    PubMed  CAS  Google Scholar 

  14. Chan, M. and Bennick, A. 2001. Proteolytic processing of a human salivary proline-rich protein precursor by proprotein convertases. Eur. J. Biochem. 268:3423–3431.

    Article  PubMed  CAS  Google Scholar 

  15. Chung-MacCoubrey, A. L., Hagerman, A. E., and Kirkpatrick, R. L. 1997. Effect of tannins on digestion and detoxification activity in gray squirrels (Sciurus carolinensis). Physiol. Zool. 70:270–277.

    PubMed  CAS  Google Scholar 

  16. Clausen, T. P., Provenza, F. D., Burritt, E. A., Reichardt, P. B., and Bryant, J. P. 1990. Ecological implications of condensed tannin structure: a case study. J. Chem. Ecol. 16:2381–2392.

    Article  CAS  Google Scholar 

  17. Clauss, M., Lason, K., Gehrke, J., Lechner-Doll, M., Fickel, J., Grune, T., and Streich, W. J. 2003. Captive roe deer (Capreolus capreolus) select for low amounts of tannic acid but not quebracho: fluctuation of preferences and potential benefits. Comp. Biochem. Physiol. B 136:369–382.

    Article  PubMed  CAS  Google Scholar 

  18. Clauss, M., Gehrke, J., Hatt, J.-M., Dierenfeld, E. S., Flach, E. J., Hermes, R., Castell, J., Streich, W. J., and Fickel, J. 2005. Tannin-binding salivary proteins in three captive rhinoceros species. Comp. Biochem. Physiol. A 140:67–72.

    Article  CAS  Google Scholar 

  19. Clements, S., Mehansho, H., and Carlson, D. M. 1985. Novel multigene families encoding highly repetitive peptide sequences—sequence analyses of rat and mouse proline-rich protein cDNAs. J. Biol. Chem. 260:3471–3477.

    Google Scholar 

  20. Cooper, S. M. and Owen-Smith, N. 1985. Condensed tannins deter feeding by browsing ruminants in a South African savanna. Oecologia (Berlin) 67:142–146.

    Article  Google Scholar 

  21. Dearing, M. D. 1997. The manipulation of plant toxins by a food-hoarding herbivore, Ochotona princeps. Ecology 78:774–781.

    Article  Google Scholar 

  22. Dearing, M. D. and Cork, S. 1999. Role of detoxification of plant secondary compounds on diet breadth in a mammalian herbivore, Trichosurus vulpecula. J. Chem. Ecol. 25:1205–1220.

    Article  CAS  Google Scholar 

  23. Dearing, M. D., Foley, W. J., and McLean, S. 2005. The influence of plant secondary metabolites on the nutritional ecology of herbivorous terrestrial vertebrates. Annu. Rev. Ecol. Evol. Syst. 36:169–189.

    Article  Google Scholar 

  24. Dietz, B. A., Hagerman, A. E., and Barrett, G. W. 1994. Role of condensed tannin on salivary tannin-binding proteins, bioenergetics, and nitrogen digestibility in Microtus pennsylvanicus. J. Mammal. 75:880–889.

    Article  Google Scholar 

  25. Ferreira, F. D., Robinson, R., Hand, A. R., and Bennick, A. 1992. Differential expression of proline-rich proteins in rabbit salivary glands. J. Histochem. Cytochem. 40:1393–1404.

    PubMed  CAS  Google Scholar 

  26. Fickel, J., Goritz, F., Joest, B. A., Hildebrandt, T., Hofmann, R. R., and Breves, G. 1998. Analysis of parotid and mixed saliva in roe deer (Capreolus capreolus L.). J. Comp. Physiol. B 168:257–264.

    Article  PubMed  CAS  Google Scholar 

  27. Foley, W. J. and Moore, B. D. 2005. Plant secondary metabolites and vertebrate herbivores—from physiological regulation to ecosystem function. Curr. Opin. Plant Biol. 8:430–435.

    Article  PubMed  CAS  Google Scholar 

  28. Fowler, M. E. and Richards, W. P. C. 1965. Acorn poisoning in a cow and a sheep. J. Am. Vet. Med. 147:1215–1220.

    CAS  Google Scholar 

  29. Gehrke, J. 2001. Investigations of tannin-binding salivary proteins of roe deer and other ruminants. PhD dissertation, University of Potsdam, Potsdam (in German with English summary).

  30. Glendinning, J. I. 1992. Effect of salivary proline-rich proteins on ingestive responses to tannic acid in mice. Chem. Senses 17:1–12.

    Article  CAS  Google Scholar 

  31. Hagerman, A. E. and Butler, L. G. 1981. The specificity of proanthocyanidin–protein interactions. J. Biol. Chem. 256:4494–4497.

    PubMed  CAS  Google Scholar 

  32. Hagerman, A. E. and Robbins, C. T. 1993. Specificity of tannin-binding salivary proteins relative to diet selection by mammals. Can. J. Zool. 71:628–633.

    CAS  Article  Google Scholar 

  33. Haghighat, M., Moetamed, A., Vaseghi, T., and Aminlari, M. 1996. Isoprenaline induces biosynthesis of proline-rich proteins in the salivary glands of rat but not in sheep. Comp. Biochem. Physiol. C 115:165–168.

    PubMed  CAS  Google Scholar 

  34. Isemura, S. 2003. Salivary proline-rich proteins: protein structure, gene structure, and function. Curr. Top. Biochem. Res. 5:141–147.

    Google Scholar 

  35. Jansman, A. J. M., Frohlich, A. A., and Marquardt, R. R. 1994. Production of proline-rich proteins by the parotid glands of rats is enhanced by feeding diets containing tannins from Faba beans (Vicia faba L). J. Nutr. 124:249–258.

    PubMed  CAS  Google Scholar 

  36. Juntheikki, M.-R. 1996. Comparison of tannin-binding proteins in saliva of Scandinavian and North American moose (Alces alces). Biochem. Syst. Ecol. 24:595–601.

    Article  CAS  Google Scholar 

  37. Juntheikki, M.-R., Julkunen-Tiitto, R., and Hagerman, A. E. 1996. Salivary tannin-binding proteins in root vole (Microtus oeconomus Pallas). Biochem. Syst. Ecol. 24:25–35.

    Article  CAS  Google Scholar 

  38. Kauffman, D. L. and Keller, P. J. 1979. The basic proline-rich proteins from a single subject. Arch. Oral Biol. 24:249–256.

    Article  PubMed  CAS  Google Scholar 

  39. Kim, H. S. and Maeda, N. 1986. Structures of two HAEIII-type genes in the human salivary proline-rich protein multigene family. J. Biol. Chem. 261:6712–6718.

    PubMed  CAS  Google Scholar 

  40. Lu, Y. and Bennick, A. 1998. Interaction of tannin with human salivary proline-rich proteins. Arch. Oral Biol. 43:717–728.

    Article  PubMed  CAS  Google Scholar 

  41. Lyons, K. M., Azen, E. A., Goodman, P. A., and Smithies, O. 1988. Many protein products from a few loci: assignment of human salivary proline-rich proteins to specific loci. Genetics 120:255–265.

    PubMed  CAS  Google Scholar 

  42. Maeda, N. 1985. Inheritance of the human salivary proline-rich proteins—a reinterpretation in terms of 6 loci forming 2 subfamilies. Biochem. Genet. 23:455–464.

    Article  PubMed  CAS  Google Scholar 

  43. Maeda, N., Kim, H. S., Azen, E. A., and Smithies, O. 1985. Differential RNA splicing and post-translational cleavages in the human salivary proline-rich protein gene system. J. Biol. Chem. 260:1123–1130.

    Google Scholar 

  44. Makkar, H. P. S. and Becker, K. 1998. Adaptation of cattle to tannins: role of proline-rich proteins in oak-fed cattle. Anim. Sci. 67:277–281.

    CAS  Article  Google Scholar 

  45. Mandel, I. D., Thompson, R. H. J., and Ellison, S. A. 1965. Studies on the mucoproteins of human parotid saliva. Arch. Oral Biol. 10:499–507.

    Article  PubMed  CAS  Google Scholar 

  46. McArthur, C., Hagerman, A., and Robbins, C. T. 1991. Physiological strategies of mammalian herbivores against plant defenses, pp. 103–114, in R. T. Palo and C. T. Robbins (eds.). Plant Defences Against Mammalian Herbivory. CRC Press, Florida.

    Google Scholar 

  47. McArthur, C., Sanson, G. D., and Beal, A. M. 1995. Salivary proline-rich proteins in mammals—roles in oral homeostasis and counteracting dietary tannin. J. Chem. Ecol. 21:663–691.

    Article  CAS  Google Scholar 

  48. Mehansho, H. and Carlson, D. M. 1983. Induction of protein and glycoprotein synthesis in rat submandibular glands by isoproterenol. J. Biol. Chem. 258:6616–6620.

    PubMed  CAS  Google Scholar 

  49. Mehansho, H., Hagerman, A., Clements, S., Butler, L., Rogler, J., and Carlson, D. M. 1983. Modulation of proline-rich protein biosynthesis in rat parotid glands by sorghums with high tannin levels. Proc. Natl. Acad. Sci. USA 80:3948–3952.

    PubMed  Article  CAS  Google Scholar 

  50. Mehansho, H., Clements, S., Sheares, B. T., Smith, S., and Carlson, D. M. 1985. Induction of proline-rich glycoprotein synthesis in mouse salivary glands by isoproterenol and by tannins. J. Biol. Chem. 260:4418–4423.

    PubMed  CAS  Google Scholar 

  51. Mehansho, H., Ann, D. K., Butler, L. G., Rogler, J., and Carlson, D. M. 1987a. Induction of proline-rich proteins in hamster salivary glands by isoproterenol treatment and an unusual growth inhibition by tannins. J. Biol. Chem. 262:12344–12350.

    PubMed  CAS  Google Scholar 

  52. Mehansho, H., Butler, L. G., and Carlson, D. M. 1987b. Dietary tannins and salivary proline-rich proteins—interactions, induction, and defense mechanisms. Annu. Rev. Nutr. 7:423–440.

    Article  PubMed  CAS  Google Scholar 

  53. Mitaru, B. N., Reichert, R. D., and Blair, R. 1984. The binding of dietary protein by sorghum tannins in the digestive tract of pigs. J. Nutr. 114:1787–1796.

    PubMed  CAS  Google Scholar 

  54. Mole, S., Butler, L. G., and Iason, G. 1990. Defense against dietary tannin in herbivores—a survey for proline-rich salivary proteins in mammals. Biochem. Syst. Ecol. 18:287–293.

    Article  CAS  Google Scholar 

  55. Mole, S., Rogler, J. C., and Butler, L. G. 1993. Growth reduction by dietary tannins—different effects due to different tannins. Biochem. Syst. Ecol. 21:667–677.

    Article  CAS  Google Scholar 

  56. Muenzer, J., Bildstein, C., Gleason, M., and Carlson, D. M. 1979. Properties of proline-rich proteins from parotid glands of isoproterenol-treated rats. J. Biol. Chem. 254:5629–5634.

    PubMed  CAS  Google Scholar 

  57. Murray, N. J. and Williamson, M. P. 1994. Conformational study of a salivary proline-rich protein repeat sequence. Eur. J. Biochem. 219:915–921.

    Article  PubMed  CAS  Google Scholar 

  58. Niho, N., Shibutani, M., Tamura, T., Toyoda, K., Uneyama, C., Takahashi, N., and Hirose, M. 2001. Subchronic toxicity study of gallic acid by oral administration in F344 rats. Food Chem. Toxicol. 39:1063–1070.

    Article  PubMed  CAS  Google Scholar 

  59. Oppenheim, F. G., Hay, D. I., and Franzblau, C. 1971. Proline-rich proteins from human parotid saliva. I. Isolation and partial characterization. Biochemistry. 10:4233–4238.

    Article  PubMed  CAS  Google Scholar 

  60. Oppenheim, F. G., Kousvelari, E. E., and Troxler, R. F. 1979. Immunological cross-reactivity and sequence homology between salivary proline-rich proteins in human and macaque monkey (Macaca fascicularis) parotid saliva. Arch. Oral Biol. 24:595–599.

    Article  PubMed  CAS  Google Scholar 

  61. Oppenheim, F. G., Hay, D. I., Smith, D. J., Offner, G. D., and Troxler, R. F. 1987. Molecular basis of salivary proline-rich protein and peptide synthesis—cell-free translations and processing of human and macaque statherin messenger-RNAs and partial amino-acid-sequence of their signal peptides. J. Dent. Res. 66:462–466.

    PubMed  CAS  Google Scholar 

  62. Robbins, C. T., Hanley, T. A., Hagerman, A. E., Hjeljord, O., Baker, D. L., Schwartz, C. C., and Mautz, W. W. 1987. Role of tannins in defending plants against ruminants: reduction in protein availability. Ecology 68:98–107.

    Article  CAS  Google Scholar 

  63. Robbins, C. T., Hagerman, A. E., Austin, P. J., McArthur, C., and Hanley, T. A. 1991. Variation in mammalian physiological responses to a condensed tannin and its ecological implications. J. Mammal. 72:480–486.

    Article  Google Scholar 

  64. Sabatini, L. M., Warner, T. F., Saitoh, E., and Azen, E. A. 1989. Tissue distribution of RNAs for cystatins, histatins, statherin, and proline-rich salivary proteins in human and macaques. J. Dent. Res. 68:1138–1145.

    PubMed  CAS  Google Scholar 

  65. Schmidt-Nielsen, K. 1997. Animal Physiology. Cambridge University Press, Cambridge.

    Google Scholar 

  66. Schulz, G. E. and Schirmer, R. H. 1979. Principles of Protein Structure. Springer, Berlin.

    Google Scholar 

  67. Shimada, T. 2001. Hoarding behaviors of two wood mouse species: different preference for acorns of two Fagaceae species. Ecol. Res. 16:127–133.

    Article  Google Scholar 

  68. Shimada, T. and Saitoh, T. 2003. Negative effects of acorns on the wood mouse Apodemus speciosus. Pop. Ecol. 45:7–17.

    Google Scholar 

  69. Shimada, T., Saitoh, T., and Matsui, T. 2004. Does acclimation reduce the negative effects of acorn tannins in the wood mouse Apodemus speciosus? Acta Theriol. 49:203–214.

    Google Scholar 

  70. Shimada, T., Saitoh, T., Sasaki, E., Nishitani, Y., and Osawa, R. 2006. The role of tannin-binding salivary proteins and tannase-producing bacteria in the acclimation of the japanese wood mouse to accorn tannins. J. Chem. Ecol. (in press).

  71. Skopec, M. M., Hagerman, A. E., and Karasov, W. H. 2004. Do salivary proline-rich proteins counteract dietary hydrolyzable tannin in laboratory rats? J. Chem. Ecol. 30:1679–1692.

    Article  PubMed  CAS  Google Scholar 

  72. Sowell, B. F., Koerth, B. H., and Bryant, F. C. 1985. Seasonal nutrient estimates of mule deer diets in the Texas Panhandle. J. Range Manage. 38:163–167.

    Article  Google Scholar 

  73. Sugiyama, K. and Ogata, K. 1993. High performance liquid chromatographic determination of histatins in human saliva. J. Chromatogr. 619:306–309.

    PubMed  Article  CAS  Google Scholar 

  74. Takemoto, H. 2003. Phytochemical determination for leaf food choice by wild chimpanzees in Guinea, Bossou. J. Chem. Ecol. 29:2551–2573.

    Article  PubMed  CAS  Google Scholar 

  75. Tatsukawa, K. and Murakami, O. 1976. On the food utilization of the Japanese wood mouse Apodemus speciosus (Mammalia: Muridae). Physiol. Ecol. Jpn. 17:133–144.

    Google Scholar 

  76. Vaithiyanathan, S., Mishra, J. P., Sheikh, Q., and Kumar, R. 2001. Salivary gland tannins binding proteins of sheep and goat. Ind. J. Anim. Sci. 71:1131–1134.

    Google Scholar 

  77. Waterman, P. G. and Mole, S. 1994. Analysis of Phenolic Plant Metabolites. Blackwell, Oxford.

    Google Scholar 

  78. Yan, Q. Y. and Bennick, A. 1995. Identification of histatins as tannin-binding proteins in human saliva. Biochem. J. 311:341–347.

    PubMed  CAS  Google Scholar 

  79. Ziemer, M. A., Swain, W. F., Rutter, W. J., Clements, S., Ann, D. K., and Carlson, D. M. 1984. Nucleotide-sequence analysis of a proline-rich protein cDNA and peptide homologies of rat and human proline-rich proteins. J. Biol. Chem. 259:475–480.

    PubMed  Google Scholar 

  80. Zucker, W. V. 1983. Tannins: does structure determine function? An ecological perspective. Am. Nat. 121:335–365.

    Article  CAS  Google Scholar 

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Acknowledgments

I am grateful to T. Saitoh, T. Matsui, and R. Osawa for helpful discussions, two anonymous reviewers for useful comments, and Bill Foley for offering me the chance to write this review. This study was supported in part by Grants-in-Aid (no. 17570027) from the Ministry of Education, Science and Culture of Japan.

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Correspondence to Takuya Shimada.

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Shimada, T. Salivary Proteins as a Defense Against Dietary Tannins. J Chem Ecol 32, 1149–1163 (2006). https://doi.org/10.1007/s10886-006-9077-0

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Keywords

  • Affinity to tannins
  • Defense mechanisms against tannins
  • Feeding niche
  • Histatins
  • Nitrogen costs
  • Proline-rich proteins (PRPs)