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Synthetic Coprisin Analog Peptide, D-CopA3 has Antimicrobial Activity and Pro-Apoptotic Effects in Human Leukemia Cells

  • Kim, Soon-Ja (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Kim, In-Woo (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Kwon, Yong-Nam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Yun, Eun-Young (Department of Agricultural Biology, National Academy of Agricultural Science, RDA) ;
  • Hwang, Jae-Sam (Department of Agricultural Biology, National Academy of Agricultural Science, RDA)
  • Received : 2011.10.21
  • Accepted : 2011.11.01
  • Published : 2012.02.28

Abstract

Recently, we reported that the synthetic Coprisin analog peptide 9-mer dimer CopA3 (consisted of all-L amino acid sequence) was designed based on a defensin-like peptide, Coprisin isolated from Copris tripartitus. The 9-mer dimer CopA3 (L-CopA3) had antibacterial activity and induced apoptosis in human leukemia cells via a caspase-independent pathway. In this study, all of amino acid sequences of L-CopA3 were modified to all D-form amino acids (DCopA3) to develop a more effective antimicrobial peptide. We investigated whether D-CopA3 had antimicrobial activities against pathogenic microorganisms and pro-apoptotic effects in human leukemia cells (U937, Jurkat, and AML-2). The synthetic peptide D-CopA3 had antimicrobial activities against various pathogenic bacteria and yeast fungus with MIC values in the 4~64 ${\mu}M$ range. Moreover, D-CopA3 caused cell growth inhibition, and increased the chromosomal DNA fragmentation and the expression of inflammatory cytokines, TNF-${\alpha}$ and IL1-${\beta}$, transcripts in human leukemia cells. The all-D amino acid peptide DCopA3 proved as effective as the L-CopA3 reported previously. These results provide the basis for developing D-CopA3 as a new antibiotic peptide.

Keywords

References

  1. Baker, M. A., W. L. Maloy, M. Zasloff, and L. S. Jacob. 1993. Anticancer efficacy of Magainin2 and analogue peptides. Cancer Res. 53: 3052-3057.
  2. Bessalle, R., A. Kapitkovsky, A. Gorea, I. Shalit, and M. Fridkin. 1990. All-D-magainin: Chirality, antimicrobial activity and proteolytic resistance. FEBS Lett. 274: 151-155. https://doi.org/10.1016/0014-5793(90)81351-N
  3. Boman, H. G. 2003. Antibacterial peptides: Basic facts and emerging concepts. J. Intern. Med. 254: 197-215. https://doi.org/10.1046/j.1365-2796.2003.01228.x
  4. Braunstein, A., N. Papo, and Y. Shai. 2004. In vitro activity and potency of an intravenously injected antimicrobial peptide and its DL amino acid analog in mice infected with bacteria. Antimicrob. Agents Chemother. 48: 3127-3129. https://doi.org/10.1128/AAC.48.8.3127-3129.2004
  5. Bulet, P., S. Cociancich, M. Reuland, F. Sauber, R. Bischoff, G. Hegy, et al. 1992. A novel insect defensin mediates the inducible antibacterial activity in larvae of the dragonfly Aeschna cyanea (Paleoptera, Odonata). Eur. J. Biochem. 209: 977-984. https://doi.org/10.1111/j.1432-1033.1992.tb17371.x
  6. Bulet, P., C. Hetru, J. L. Dimarcq, and D. Hoffmann. 1999. Antimicrobial peptides in insects; structure and function. Dev. Comp. Immunol. 23: 329-344. https://doi.org/10.1016/S0145-305X(99)00015-4
  7. Bulet, P. and R. Stocklin. 2005. Insect antimicrobial peptides: Structures, properties and gene regulation. Protein Pept. Lett. 12: 3-11. https://doi.org/10.2174/0929866053406011
  8. Dempsey, C. E. 1990. The actions of melittin on membranes. Biochim. Biophys. Acta 1031: 143-161. https://doi.org/10.1016/0304-4157(90)90006-X
  9. Grethe, S., M. P. Ares, T. Andersson, and M. I. Porn-Ares. 2004. p38 MAPK mediates TNF-induced apoptosis in endothelial cells via phosphorylation and downregulation of Bcl-x(L). Exp. Cell Res. 298: 632-642. https://doi.org/10.1016/j.yexcr.2004.05.007
  10. Hancock, R. E. and M. G. Scott. 2000. The role of antimicrobial peptides in animal defenses. Proc. Natl. Acad. Sci. USA 97: 8856-8861. https://doi.org/10.1073/pnas.97.16.8856
  11. Hwang, J. S., J. Lee, Y. J. Kim, H. S. Bang, E. Y. Yun, S. R. Kim, et al. 2009. Isolation and characterization of a defensinlike peptide (Coprisin) from the dung beetle, Copris tripartitus. Int. J. Pept. DOI: 10.1155/2009/136284.
  12. Iwasaki, T., J. Ishibashi, H. Tanaka, M. Sato, A. Asaoka, D. Taylor, and M. Yamakawa. 2009. Selective cancer cell cytotoxicity of enantiomeric 9-mer peptides derived from beetle defensins depends on negatively charged phosphatidylserine on the cell surface. Peptides 30: 660-668. https://doi.org/10.1016/j.peptides.2008.12.019
  13. Kang, J. K., J. S. Hwang, H. J. Nam, K. J. Ahn, H. Seok, S. K. Kim, et al. 2011. The insect peptide Coprisin prevents Clostridium difficile-mediated acute inflammation and mucosal damage through selective antimicrobial activity. Antimicrob. Agents Chemother. 55: 4850-4857. https://doi.org/10.1128/AAC.00177-11
  14. Matsuyama, K. and S. Natori. 1988. Purification of three antibacterial proteins from the culture medium of NIH-Sape-4, an embryonic cell line of Sarcophaga peregrina. J. Biol. Chem. 263: 17112-17116.
  15. Moore, A. J., D. A. Devine, and M. C. Bibby. 1994. Preliminary experimental anticancer activity of cecropins. Pept. Res. 7: 265-269.
  16. Papo, N., A. Braunstein, Z. Eshhar, and Y. Shai. 2004. Suppression of human prostate tumor growth in mice by a cytolytic D-, L-amino acid peptide: Membrane lysis, increased necrosis, and inhibition of prostate-specific antigen secretion. Cancer Res. 64: 5779-5786. https://doi.org/10.1158/0008-5472.CAN-04-1438
  17. Papo, N., M. Shahar, L. Eisenbach, and Y. Shai. 2003. A novel lytic peptide composed of DL-amino acids selectively kills cancer cells in culture and in mice. J. Biol. Chem. 278: 21018- 21023. https://doi.org/10.1074/jbc.M211204200
  18. Raff, M. 1998. Cell suicide for beginners. Nature 396: 119-122. https://doi.org/10.1038/24055
  19. Saldeen, J. and N. Welsh. 2004. p38 MAPK inhibits JNK2 and mediates cytokine-activated iNOS induction and apoptosis independently of NF-KB translocation in insulin-producing cells. Eur. Cytokine Netw. 15: 47-52.
  20. Soballe, P. W., W. L. Maloy, M. L. Myrga, L. S. Jacob, and M. Herlyn. 1995. Experimental local therapy of human melanoma with lytic magainin peptides. Int. J. Cancer 60: 280-284. https://doi.org/10.1002/ijc.2910600225
  21. Thevissen, K., K. K. Ferket, I. E. Francois, and B. P. Cammue. 2003. Interactions of antifungal plant defensins with fungal membrane components. Peptides 24: 1705-1712. https://doi.org/10.1016/j.peptides.2003.09.014
  22. Tosteson, M. T., S. J. Holmes, M. Razin, and D. C. Tosteson. 1985. Melittin lysis of red cells. J. Membr. Biol. 87: 35-44. https://doi.org/10.1007/BF01870697
  23. Wade, D., A. Boman, B. Wahlin, C. M. Drain, D. Andreu, H. G. Boman, and R. B. Merrifield. 1990. All-D amino acid-containing channel-forming antibiotic peptides. Proc. Natl. Acad. Sci. USA 87: 4761-4765. https://doi.org/10.1073/pnas.87.12.4761
  24. Wyllie, A. H. 1997. Apoptosis: An overview. Br. Med. Bull. 53: 451-465. https://doi.org/10.1093/oxfordjournals.bmb.a011623
  25. Xiao, Y. C., Y. D. Huang, P. L. Xu, Z. Q. Zhou, and X. K. Li. 2006. Pro-apoptotic effect of cecropin AD on nasopharyngeal carcinoma cells. Chin. Med. J. (Engl.) 119: 1042-1046.
  26. Zasloff, M. 1992. Antibiotic peptides as mediators of innate immunity. Curr. Opin. Immunol. 4: 3-7. https://doi.org/10.1016/0952-7915(92)90115-U

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