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BioMed Research International
Volume 2013 (2013), Article ID 103494, 12 pages
http://dx.doi.org/10.1155/2013/103494
Research Article

Chemical Modifications of PhTX-I Myotoxin from Porthidium hyoprora Snake Venom: Effects on Structural, Enzymatic, and Pharmacological Properties

1Department of Biochemistry, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, 13083-970 Campinas, SP, Brazil
2Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), Campinas, SP, Brazil
3Biotechnology Laboratory (LABIOTEC), Department of Biochemistry, Institute of Biology, University of Campinas (UNICAMP), Campinas, SP, Brazil
4National Institute of Science and Technology for Structural Biology and Bioimaging, Rio de Janeiro, RJ, Brazil

Received 17 September 2012; Accepted 31 October 2012

Academic Editor: Elen Cristina Teizem Landucci

Copyright © 2013 Salomón Huancahuire-Vega et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. R. M. Kini, “Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes,” Toxicon, vol. 42, no. 8, pp. 827–840, 2003. View at Publisher · View at Google Scholar · View at Scopus
  2. J. Pungerčar and I. Križaj, “Understanding the molecular mechanism underlying the presynaptic toxicity of secreted phospholipases A2,” Toxicon, vol. 50, no. 7, pp. 871–892, 2007. View at Publisher · View at Google Scholar · View at Scopus
  3. J. M. Gutiérrez, L. A. Ponce-Soto, S. Marangoni, and B. Lomonte, “Systemic and local myotoxicity induced by snake venom group II phospholipases A2: comparison between crotoxin, crotoxin B and a Lys49 PLA2 homologue,” Toxicon, vol. 51, no. 1, pp. 80–92, 2008. View at Publisher · View at Google Scholar · View at Scopus
  4. D. A. Warrell, “Snake bite,” The Lancet, vol. 375, no. 9708, pp. 77–88, 2010. View at Publisher · View at Google Scholar · View at Scopus
  5. M. Z. Huang, Q. C. Wang, and G. F. Liu, “Effects of an acidic phospholipase A2 purified from Ophiophagus hannah (king cobra) venom on rat heart,” Toxicon, vol. 31, no. 5, pp. 627–635, 1993. View at Publisher · View at Google Scholar · View at Scopus
  6. V. N. Atanasov, D. Danchev, M. Mitewa, and S. Petrova, “Hemolytic and anticoagulant study of the neurotoxin vipoxin and its components-basic phospholipase A2 and an acidic inhibitor,” Biochemistry, vol. 74, no. 3, pp. 276–280, 2009. View at Publisher · View at Google Scholar · View at Scopus
  7. L. M. S. Rudrammaji, K. D. Machiah, T. P. K. Kantha, and T. V. Gowda, “Role of catalytic function in the antiplatelet activity of phospholipase A2 cobra (Naja naja naja) venom,” Molecular and Cellular Biochemistry, vol. 219, no. 1-2, pp. 39–44, 2001. View at Publisher · View at Google Scholar · View at Scopus
  8. C. Cicala and G. Cirino, “Phospholipase A2-induced hypotension in the rat and its pharmacological modulation,” General Pharmacology, vol. 24, no. 5, pp. 1197–1202, 1993. View at Scopus
  9. B. R. Francis, N. J. da Silva, C. Seebart, L. L. C. Silva, J. J. Schmidt, and I. I. Kaiser, “Toxins isolated from the venom of the Brazilian coral snake (Micrurus frontalis frontalis) include hemorrhagic type phospholipases A2 and postsynaptic neurotoxins,” Toxicon, vol. 35, no. 8, pp. 1193–1203, 1997. View at Publisher · View at Google Scholar · View at Scopus
  10. T. Ferreira, E. A. Camargo, M. T. C. P. Ribela et al., “Inflammatory oedema induced by Lachesis muta muta (Surucucu) venom and LmTX-I in the rat paw and dorsal skin,” Toxicon, vol. 53, no. 1, pp. 69–77, 2009. View at Publisher · View at Google Scholar · View at Scopus
  11. L. A. Ponce-Soto, B. Lomonte, J. M. Gutiérrez, L. Rodrigues-Simioni, J. C. Novello, and S. Marangoni, “Structural and functional properties of BaTX, a new Lys49 phospholipase A2 homologue isolated from the venom of the snake Bothrops alternatus,” Biochimica et Biophysica Acta, vol. 1770, no. 4, pp. 585–593, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. L. A. Ponce-Soto, D. Martins-de-souza, and S. Marangoni, “Neurotoxic, myotoxic and cytolytic activities of the new basic PLA2 isoforms BmjeTX-I and BmjeTX-II isolated from the Bothrops marajoensis (marajó lancehead) snake venom,” Protein Journal, vol. 29, no. 2, pp. 103–113, 2010. View at Publisher · View at Google Scholar · View at Scopus
  13. R. K. Arni and R. J. Ward, “Phospholipase A2—A structural review,” Toxicon, vol. 34, no. 8, pp. 827–841, 1996. View at Publisher · View at Google Scholar · View at Scopus
  14. T. Petan, I. Križaj, and J. Pungerčar, “Restoration of enzymatic activity in a Ser-49 phospholipase A2 homologue decreases its CA2+-independent membrane-damaging activity and increases its toxicity,” Biochemistry, vol. 46, no. 44, pp. 12795–12809, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. B. Lomonte, Y. Angulo, M. Sasa, and J. M. Gutiérrez, “The phospholipase A2 homologues of snake venoms: biological activities and their possible adaptive roles,” Protein and Peptide Letters, vol. 16, no. 8, pp. 860–876, 2009. View at Publisher · View at Google Scholar · View at Scopus
  16. S. Huancahuire-Vega, L. A. Ponce-Soto, D. Martins-de-Souza, and S. Marangoni, “Structural and functional characterization of brazilitoxins II and III (BbTX-II and -III), two myotoxins from the venom of Bothrops brazili snake,” Toxicon, vol. 54, no. 6, pp. 818–827, 2009. View at Publisher · View at Google Scholar · View at Scopus
  17. L. B. Jensen, N. K. Burgess, D. D. Gonda et al., “Mechanisms governing the level of susceptibility of erythrocyte membranes to secretory phospholipase A2,” Biophysical Journal, vol. 88, no. 4, pp. 2692–2705, 2005. View at Publisher · View at Google Scholar · View at Scopus
  18. C. M. Jenkins, A. Cedars, and R. W. Gross, “Eicosanoid signalling pathways in the heart,” Cardiovascular Research, vol. 82, no. 2, pp. 240–249, 2009. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Cintra-Francischinelli, P. Pizzo, Y. Angulo, J. M. Gutiérrez, C. Montecucco, and B. Lomonte, “The C-terminal region of a Lys49 myotoxin mediates CA2+ influx in C2C12 myotubes,” Toxicon, vol. 55, no. 2-3, pp. 590–596, 2010. View at Publisher · View at Google Scholar · View at Scopus
  20. S. Huancahuire-Vega, L. A. Ponce-Soto, D. Martins-de-Souza, and S. Marangoni, “Biochemical and pharmacological characterization of PhTX-I a new myotoxic phospholipase A2 isolated from Porthidium hyoprora snake venom,” Comparative Biochemistry and Physiology C, vol. 29, pp. 103–113, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. C. Díaz-Oreiro and J. M. Gutiérrez, “Chemical modification of histidine and lysine residues of myotoxic phospholipases A2 isolated from Bothrops asper and Bothrops godmani snake venoms: effects on enzymatic and pharmacological properties,” Toxicon, vol. 35, no. 2, pp. 241–252, 1997. View at Publisher · View at Google Scholar · View at Scopus
  22. A. M. Soares, S. H. Andrião-Escarso, R. K. Bortoleto et al., “Dissociation of enzymatic and pharmacological properties of piratoxins-I and -III, two myotoxic phospholipases A2 from Bothrops pirajai snake venom,” Archives of Biochemistry and Biophysics, vol. 387, no. 2, pp. 188–196, 2001. View at Publisher · View at Google Scholar · View at Scopus
  23. A. M. Soares and J. R. Giglio, “Chemical modifications of phospholipases A2 from snake venoms: effects on catalytic and pharmacological properties,” Toxicon, vol. 42, no. 8, pp. 855–868, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. K. R. Soons, E. Condrea, C. C. Yang, and P. Rosenberg, “Effects of modification of tyrosines 3 and 62 (63) on enzymatic and toxicological properties of phospholipases A2 from Naja nigricollis and Naja naja atra snake venoms,” Toxicon, vol. 24, no. 7, pp. 679–693, 1986. View at Scopus
  25. C. Takasaki, A. Sugama, A. Yanagita, N. Tamiya, E. G. Rowan, and A. L. Harvey, “Effects of chemical modifications of Pa-11, a phospholipase A2 from the venom of Australian king brown snake (Pseudechis australis), on its biological activities,” Toxicon, vol. 28, no. 1, pp. 107–117, 1990. View at Publisher · View at Google Scholar · View at Scopus
  26. R. L. Heinrikson and S. C. Meredith, “Amino acid analysis by reverse-phase high-performance liquid chromatography: precolumn derivatization with phenylisothiocyanate,” Analytical Biochemistry, vol. 136, no. 1, pp. 65–74, 1984. View at Scopus
  27. H. Schagger, H. Aquila, and G. Von Jagow, “Comassie blue-sodium dodecyl sulfate-polyacrylamide gel electrophoresis for direct visualization of polypeptides during electrophoresis,” Analytical Biochemistry, vol. 166, pp. 368–379, 1987. View at Scopus
  28. D. H. A. Corrêa and C. H. I. Ramos, “The use of circular dichroism spectroscopy to study protein folding, form and function,” African Journal of Biochemistry Research, vol. 3, pp. 164–173, 2009.
  29. W. Cho and F. J. Kezdy, “Chromogenic substrates and assay of phospholipases A2,” Methods in Enzymology, vol. 197, pp. 75–79, 1991. View at Scopus
  30. M. Holzer and S. P. Mackessy, “An aqueous endpoint assay of snake venom phospholipase A2,” Toxicon, vol. 34, no. 10, pp. 1149–1155, 1996. View at Publisher · View at Google Scholar · View at Scopus
  31. E. Borenfreund and O. Borrero, “In vitro cytotoxicity assays. Potential alternatives to the Draize ocular allergy test,” Cell Biology and Toxicology, vol. 1, no. 1, pp. 55–65, 1984. View at Scopus
  32. C. C. Yang and L. S. Chang, “Dissociation of lethal toxicity and enzymic activity of notexin from Notechis scutatus scutatus (Australian-tiger-snake) venom by modification of tyrosine residues,” Biochemical Journal, vol. 280, no. 3, pp. 739–744, 1991. View at Scopus
  33. A. M. Soares, R. Guerra-Sá, C. R. Borja-Oliveira et al., “Structural and functional characterization of BnSP-7, a Lys49 myotoxic phospholipase A2 homologue from Bothrops neuwiedi pauloensis venom,” Archives of Biochemistry and Biophysics, vol. 378, no. 2, pp. 201–209, 2000. View at Publisher · View at Google Scholar · View at Scopus
  34. P. Rosenburg, A. Ghassemi, E. Condrea, D. Dhillon, and C. C. Yang, “Do chemical modifications dissociate between the enzymatic and pharmacological activities of β bungarotoxin and notexin?” Toxicon, vol. 27, no. 2, pp. 137–159, 1989. View at Scopus
  35. S. H. Andrião-Escarso, A. M. Soares, V. M. Rodrigues et al., “Myotoxic phospholipases A2 in Bothrops snake venoms: effect of chemical modifications on the enzymatic and pharmacological properties of bothropstoxins from Bothrops jararacussu,” Biochimie, vol. 82, no. 8, pp. 755–763, 2000. View at Publisher · View at Google Scholar · View at Scopus
  36. A. Bazaa, J. Luis, N. Srairi-Abid et al., “MVL-PLA2, a phospholipase A2 from Macrovipera lebetina transmediterranea venom, inhibits tumor cells adhesion and migration,” Matrix Biology, vol. 28, no. 4, pp. 188–193, 2009. View at Publisher · View at Google Scholar · View at Scopus
  37. D. L. Scott, A. Achari, J. C. Vidal, and P. B. Sigler, “Crystallographic and biochemical studies of the (inactive) Lys-49 phospholipase A2 from the venom of Agkistridon piscivorus piscivorus,” Journal of Biological Chemistry, vol. 267, no. 31, pp. 22645–22657, 1992. View at Scopus
  38. P. H. Kao, K. C. Chen, S. R. Lin, and L. S. Chang, “The structural and functional contribution of N-terminal region and His-47 on Taiwan cobra phospholipase A2,” Journal of Peptide Science, vol. 14, no. 3, pp. 342–348, 2008. View at Publisher · View at Google Scholar · View at Scopus
  39. E. B. S. Diz Filho, S. Marangoni, D. O. Toyama et al., “Enzymatic and structural characterization of new PLA2 isoform isolated from white venom of Crotalus durissus ruruima,” Toxicon, vol. 53, no. 1, pp. 104–114, 2009. View at Publisher · View at Google Scholar · View at Scopus
  40. D. D. O. Toyama, E. B. D. S. Diz Filho, B. S. Cavada et al., “Umbelliferone induces changes in the structure and pharmacological activities of Bn IV, a phospholipase A2 isoform isolated from Bothrops neuwiedi,” Toxicon, vol. 57, no. 6, pp. 851–860, 2011. View at Publisher · View at Google Scholar · View at Scopus
  41. D. G. Beghini, M. H. Toyama, S. Hyslop, L. C. Sodek, Novello, and S. Marangoni, “Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus cascavella rattlesnake (Maracambóia) venom,” Journal of Protein Chemistry, vol. 19, no. 8, pp. 679–684, 2000. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Shina, S. L. Yates, A. Ghassemi, P. Rosenberg, and E. Condrea, “Inhibitory effect of EDTA·Ca2+ on the hydrolysis of synaptosomal phospholipids by phospholipase A2 toxins and enzymes,” Biochemical Pharmacology, vol. 40, no. 10, pp. 2233–2239, 1990. View at Publisher · View at Google Scholar · View at Scopus
  43. V. L. Bonfim, M. H. Toyama, J. C. Novello et al., “Isolation and enzymatic characterization of a basic phospholipase A2 from Bothrops jararacussu snake venom,” Protein Journal, vol. 20, no. 3, pp. 239–245, 2001. View at Scopus
  44. C. C. Yang, “Chemical modification and functional sites of phospholipases A2,” in Venom Phospholipase A2 Enzymes: Structure, Function and Mechanism, R. M. Kini, Ed., pp. 185–204, Wiley, Chichester, UK, 1997.
  45. J. Rangel, O. Quesada, J. M. Gutiérrez, Y. Angulo, and B. Lomonte, “Membrane cholesterol modulates the cytolytic mechanism of myotoxin II, a Lys49 phospholipase A2 homologue from the venom of Bothrops asper,” Cell Biochemistry and Function, vol. 29, no. 5, pp. 365–370, 2011. View at Publisher · View at Google Scholar · View at Scopus
  46. B. Lomonte, Y. Angulo, and L. Calderón, “An overview of lysine-49 phospholipase A2 myotoxins from crotalid snake venoms and their structural determinants of myotoxic action,” Toxicon, vol. 42, no. 8, pp. 885–901, 2003. View at Publisher · View at Google Scholar · View at Scopus
  47. Y. Angulo and B. Lomonte, “Differential susceptibility of C2C12 myoblasts and myotubes to group II phospholipase A2 myotoxins from crotalid snake venoms,” Cell Biochemistry and Function, vol. 23, no. 5, pp. 307–313, 2005. View at Publisher · View at Google Scholar · View at Scopus
  48. L. C. Gebrim, S. Marcussi, D. L. Menaldo et al., “Antitumor effects of snake venom chemically modified Lys49 phospholipase A2-like BthTX-I and a synthetic peptide derived from its C-terminal region,” Biologicals, vol. 37, no. 4, pp. 222–229, 2009. View at Publisher · View at Google Scholar · View at Scopus
  49. F. F. Romero-Vargas, L. A. Ponce-Soto, D. Martins-de-Souza, and S. Marangoni, “Biological and biochemical characterization of two new PLA2 isoforms Cdc-9 and Cdc-10 from Crotalus durissus cumanensis snake venom,” Comparative Biochemistry and Physiology C, vol. 151, no. 1, pp. 66–74, 2010. View at Publisher · View at Google Scholar · View at Scopus
  50. T. R. Costa, D. L. Menaldo, C. Z. Oliveira et al., “Myotoxic phospholipases A2 isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: cytotoxic effect on microorganism and tumor cells,” Peptides, vol. 29, no. 10, pp. 1645–1656, 2008. View at Publisher · View at Google Scholar · View at Scopus
  51. J. Cummings, C. Hodgkinson, R. Odedra et al., “Preclinical evaluation of M30 and M65 ELISAs as biomarkers of drug induced tumor cell death and antitumor activity,” Molecular Cancer Therapeutics, vol. 7, no. 3, pp. 455–463, 2008. View at Publisher · View at Google Scholar · View at Scopus
  52. S. R. Panini, L. Yang, A. E. Rusinol, M. S. Sinensky, J. V. Bonventre, and C. C. Leslie, “Arachidonate metabolism and the signaling pathway of induction of apoptosis by oxidized LDL/oxysterol,” Journal of Lipid Research, vol. 42, no. 10, pp. 1678–1686, 2001. View at Scopus
  53. C. F. P. Teixeira, E. C. T. Landucci, E. Antunes, M. Chacur, and Y. Cury, “Inflammatory effects of snake venom myotoxic phospholipases A2,” Toxicon, vol. 42, no. 8, pp. 947–962, 2003. View at Publisher · View at Google Scholar · View at Scopus
  54. C. Teixeira, Y. Cury, V. Moreira, G. Picolo, and F. Chaves, “Inflammation induced by Bothrops asper venom,” Toxicon, vol. 54, no. 7, pp. 988–997, 2009. View at Publisher · View at Google Scholar · View at Scopus
  55. J. P. Zuliani, C. M. Fernandes, S. R. Zamuner, J. M. Gutiérrez, and C. F. P. Teixeira, “Inflammatory events induced by Lys-49 and Asp-49 phospholipases A2 isolated from Bothrops asper snake venom: role of catalytic activity,” Toxicon, vol. 45, no. 3, pp. 335–346, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. B. S. Vishwanath, R. M. Kini, and T. V. Gowda, “Characterization of three edema-inducing phospholipase A2 enzymes from habu (Trimeresurus flavoviridis) venom and their interaction with the alkaloid aristolochic acid,” Toxicon, vol. 25, no. 5, pp. 501–509, 1987. View at Scopus
  57. A. M. Soares, W. P. Sestito, S. Marcussi et al., “Alkylation of myotoxic phospholipases A2 in Bothrops moojeni venom: a promising approach to an enhanced antivenom production,” International Journal of Biochemistry and Cell Biology, vol. 36, no. 2, pp. 258–270, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Zhao, L. Tang, X. Wang, Y. Zhou, and Z. Lin, “Structure of a snake venom phospholipase A2 modified by p-bromo-phenacyl-bromide,” Toxicon, vol. 36, no. 6, pp. 875–886, 1998. View at Publisher · View at Google Scholar · View at Scopus
  59. C. Araya and B. Lomonte, “Antitumor effects of cationic synthetic peptides derived from Lys49 phospholipase A2 homologues of snake venoms,” Cell Biology International, vol. 31, no. 3, pp. 263–268, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. R. G. Stábeli, S. F. Amui, C. D. Sant'Ana et al., “Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: an example of function versatility of snake venom proteins,” Comparative Biochemistry and Physiology C, vol. 142, no. 3-4, pp. 371–381, 2006. View at Publisher · View at Google Scholar · View at Scopus