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. 2004 Aug;13(4):263–268. doi: 10.1080/09629350400003068

Effects of 'casoparan', a peptide isolated from casein hydrolysates with mastoparan-like properties.

Ivo Lebrun 1, Valéria Cavallaro 1, Luiz Juliano 1, Maria A Juliano 1, Maria C C de Sousa e Silva 1
PMCID: PMC1781564  PMID: 15545057

Abstract

Casein, a protein found in milk of several species, is divided into different chains from 19 to 25 kDa. Casein is also considered as a source of amino acids and generating peptides with biological activities such as opiate, immunostimulating, antibacterial, peptidase inhibitors, among others. In this work, Sephadex G-10 chromatography followed by high-performance liquid chromatography isolation purified NZCase TT, an industrial culture media for tetanus toxin production. In the first step, four pools were isolated and tested in different assays: isolated smooth muscle assay (guinea pig ileum, rat uterus), phagocytosis in vitro of opsonized sheep red blood cells, and hydrogen peroxide (H2O2) release from mouse peritoneal macrophages. Pool III was the main active pool being able to potentiate bradykinin action in guinea pig ileum, stimulating phagocitic activity by resident macrophages and increasing H2O2 release from macrophages previously activated with bacille Calmette Guérin. Using mass spectra the primary structure of the main peptide from pool III was obtained--INKKI, which corresponds to beta-casein fragment 26-30. The immunostimulating action is probably related to a direct action in macrophage cells.

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Selected References

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  1. Adams D. O., Hamilton T. A. The cell biology of macrophage activation. Annu Rev Immunol. 1984;2:283–318. doi: 10.1146/annurev.iy.02.040184.001435. [DOI] [PubMed] [Google Scholar]
  2. Aderem A., Underhill D. M. Mechanisms of phagocytosis in macrophages. Annu Rev Immunol. 1999;17:593–623. doi: 10.1146/annurev.immunol.17.1.593. [DOI] [PubMed] [Google Scholar]
  3. Allen L. A., Aderem A. Mechanisms of phagocytosis. Curr Opin Immunol. 1996 Feb;8(1):36–40. doi: 10.1016/s0952-7915(96)80102-6. [DOI] [PubMed] [Google Scholar]
  4. Argiolas A., Pisano J. J. Isolation and characterization of two new peptides, mastoparan C and crabrolin, from the venom of the European hornet, Vespa crabro. J Biol Chem. 1984 Aug 25;259(16):10106–10111. [PubMed] [Google Scholar]
  5. Bogdan C., Röllinghoff M., Diefenbach A. Reactive oxygen and reactive nitrogen intermediates in innate and specific immunity. Curr Opin Immunol. 2000 Feb;12(1):64–76. doi: 10.1016/s0952-7915(99)00052-7. [DOI] [PubMed] [Google Scholar]
  6. Castagna M., Takai Y., Kaibuchi K., Sano K., Kikkawa U., Nishizuka Y. Direct activation of calcium-activated, phospholipid-dependent protein kinase by tumor-promoting phorbol esters. J Biol Chem. 1982 Jul 10;257(13):7847–7851. [PubMed] [Google Scholar]
  7. Fiat A. M., Migliore-Samour D., Jollès P., Drouet L., Bal dit Sollier C., Caen J. Biologically active peptides from milk proteins with emphasis on two examples concerning antithrombotic and immunomodulating activities. J Dairy Sci. 1993 Jan;76(1):301–310. doi: 10.3168/jds.s0022-0302(93)77351-8. [DOI] [PubMed] [Google Scholar]
  8. Gattegno L., Migliore-Samour D., Saffar L., Jollès P. Enhancement of phagocytic activity of human monocytic-macrophagic cells by immunostimulating peptides from human casein. Immunol Lett. 1988 May;18(1):27–31. doi: 10.1016/0165-2478(88)90065-x. [DOI] [PubMed] [Google Scholar]
  9. Heinrikson R. L., Meredith S. C. Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate. Anal Biochem. 1984 Jan;136(1):65–74. doi: 10.1016/0003-2697(84)90307-5. [DOI] [PubMed] [Google Scholar]
  10. Ho C. L., Lin Y. L., Chen W. C., Hwang L. L., Yu H. M., Wang K. T. Structural requirements for the edema-inducing and hemolytic activities of mastoparan B isolated from the hornet (Vespa basalis) venom. Toxicon. 1996 Sep;34(9):1027–1035. doi: 10.1016/0041-0101(96)00046-3. [DOI] [PubMed] [Google Scholar]
  11. Jollès P., Parker F., Floc'h F., Migliore D., Alliel P., Zerial A., Werner G. H. Immunostimulating substances from human casein. J Immunopharmacol. 1981;3(3-4):363–369. doi: 10.3109/08923978109031067. [DOI] [PubMed] [Google Scholar]
  12. Juliano M. A., Juliano L. Synthesis and kinetic parameters of hydrolysis by trypsin of some acyl-arginyl-p-nitroanilides and peptides containing arginyl-p-nitroanilide. Braz J Med Biol Res. 1985;18(4):435–445. [PubMed] [Google Scholar]
  13. Kayser H., Meisel H. Stimulation of human peripheral blood lymphocytes by bioactive peptides derived from bovine milk proteins. FEBS Lett. 1996 Mar 25;383(1-2):18–20. doi: 10.1016/0014-5793(96)00207-4. [DOI] [PubMed] [Google Scholar]
  14. Konno K., Hisada M., Naoki H., Itagaki Y., Kawai N., Miwa A., Yasuhara T., Morimoto Y., Nakata Y. Structure and biological activities of eumenine mastoparan-AF (EMP-AF), a new mast cell degranulating peptide in the venom of the solitary wasp (Anterhynchium flavomarginatum micado). Toxicon. 2000 Nov;38(11):1505–1515. doi: 10.1016/s0041-0101(00)00083-0. [DOI] [PubMed] [Google Scholar]
  15. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  16. Lebrun I., Lebrun F. L., Henriques O. B., Carmona A. K., Juliano L., Camargo A. C. Isolation and characterization of a new bradykinin potentiating octapeptide from gamma-casein. Can J Physiol Pharmacol. 1995 Jan;73(1):85–91. doi: 10.1139/y95-012. [DOI] [PubMed] [Google Scholar]
  17. Meisel H. Biochemical properties of regulatory peptides derived from milk proteins. Biopolymers. 1997;43(2):119–128. doi: 10.1002/(SICI)1097-0282(1997)43:2<119::AID-BIP4>3.0.CO;2-Y. [DOI] [PubMed] [Google Scholar]
  18. Migliore-Samour D., Jollès P. Casein, a prohormone with an immunomodulating role for the newborn? Experientia. 1988 Mar 15;44(3):188–193. doi: 10.1007/BF01941703. [DOI] [PubMed] [Google Scholar]
  19. Niedel J. E., Kuhn L. J., Vandenbark G. R. Phorbol diester receptor copurifies with protein kinase C. Proc Natl Acad Sci U S A. 1983 Jan;80(1):36–40. doi: 10.1073/pnas.80.1.36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Parker F., Migliore-Samour D., Floc'h F., Zerial A., Werner G. H., Jollès J., Casaretto M., Zahn H., Jollès P. Immunostimulating hexapeptide from human casein: amino acid sequence, synthesis and biological properties. Eur J Biochem. 1984 Dec 17;145(3):677–682. doi: 10.1111/j.1432-1033.1984.tb08609.x. [DOI] [PubMed] [Google Scholar]
  21. Pick E., Mizel D. Rapid microassays for the measurement of superoxide and hydrogen peroxide production by macrophages in culture using an automatic enzyme immunoassay reader. J Immunol Methods. 1981;46(2):211–226. doi: 10.1016/0022-1759(81)90138-1. [DOI] [PubMed] [Google Scholar]
  22. Rabinovitch M., DeStefano M. J. Macrophage spreading in vitro. I. Inducers of spreading. Exp Cell Res. 1973 Mar 15;77(1):323–334. doi: 10.1016/0014-4827(73)90584-3. [DOI] [PubMed] [Google Scholar]
  23. Schlimme E., Meisel H. Bioactive peptides derived from milk proteins. Structural, physiological and analytical aspects. Nahrung. 1995;39(1):1–20. doi: 10.1002/food.19950390102. [DOI] [PubMed] [Google Scholar]
  24. Wong C. W., Seow H. F., Liu A. H., Husband A. J., Smithers G. W., Watson D. L. Modulation of immune responses by bovine beta-casein. Immunol Cell Biol. 1996 Aug;74(4):323–329. doi: 10.1038/icb.1996.58. [DOI] [PubMed] [Google Scholar]
  25. Yamamoto N. Antihypertensive peptides derived from food proteins. Biopolymers. 1997;43(2):129–134. doi: 10.1002/(SICI)1097-0282(1997)43:2<129::AID-BIP5>3.0.CO;2-X. [DOI] [PubMed] [Google Scholar]
  26. van Furth R. Origin and turnover of monocytes and macrophages. Curr Top Pathol. 1989;79:125–150. [PubMed] [Google Scholar]

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