Isolation, Biochemical Characterization and Antiparasitic Activity of BmatTX-IV, A Basic Lys49-Phospholipase A2 from the Venom of Bothrops mattogrossensis from Paraguay

Author(s): Jorge Javier Alfonso, Anderson M. Kayano, Ana Fidelina Gómez Garay, Rodrigo Simões-Silva, Juliana C. Sobrinho, Santiago Vourliotis, Andreimar M. Soares, Leonardo A. Calderon, Maria Celeste Vega Gómez*.

Journal Name: Current Topics in Medicinal Chemistry

Volume 19 , Issue 22 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Functional and structural diversity of proteins of snake venoms is coupled with a wide repertoire of pharmacological effects. Snake venoms are targets of studies linked to searching molecules with biotechnological potential.

Methods: A homologue phospholipase A2 (BmatTX-IV) was obtained using two chromatographic techniques. Mass spectrometry and two-dimensional gel electrophoresis were used to determine the molecular mass and isoelectric point, respectively. By means of Edman degradation chemistry, it was possible to obtain the partial sequence of amino acids that comprise the isolated toxin. Trypanocidal, leishmanicidal and cytoxic activity against Trypanosoma cruzi, Leishmania infantum and murine fibrobasts was determinated.

Results: Combination of both chromatographic steps used in this study demonstrated efficacy to obtain the PLA2-Lys49. BmatTX-IV showed molecular mass and isoelectric point of 13.55 kDa and 9.3, respectively. Amino acid sequence of N-terminal region (51 residues) shows the presence of Lys49 residue at position 49, a distinctive trait of enzymatically inactive PLA2. Bothrops mattogrossensis snake venom showed IC50 values of 11.9 μg/mL against Leishmania infantum promastigotes and of 13.8 μg/mL against Trypanosoma cruzi epimastigotes, respectively. On the other hand, the venom showed a high cytotoxic activity (IC50 value of 16.7 μg/mL) against murine fibroblasts, whereas the BmatTX-IV showed IC50 value of 81.2 μg/mL.

Conclusion: Physicochemical and biological characterization of snake venoms components is critically important, since these complex mixtures provide a source of molecules with antiparasitic potential, making further studies necessary to identify and characterize components with higher efficacy and selectivity.

Keywords: Bothrops mattogrossensis, Snake venom, PLA2-Lys49, Antiparasitic activity, Cytotoxicity, Homologue.

[1]
Lomonte, B.; Fernández, J.; Sanz, L.; Angulo, Y.; Sasa, M.; Gutiérrez, J.M.; Calvete, J.J. Venomous snakes of Costa Rica: Biological and medical implications of their venom proteomic profiles analyzed through the strategy of snake venomics. J. Proteomics, 2014, 105, 323-339.
[http://dx.doi.org/10.1016/j.jprot.2014.02.020] [PMID: 24576642]
[2]
Simoes-Silva, R.; Alfonso, J.; Gomez, A.; Holanda, R.J.; Sobrinho, J.C.; Zaqueo, K.D.; Moreira-Dill, L.S.; Kayano, A.M.; Grabner, F.P.; da Silva, S.L.; Almeida, J.R.; Stabeli, R.G.; Zuliani, J.P.; Soares, A.M. Snake venom, A natural library of new potential therapeutic molecules: Challenges and current perspectives. Curr. Pharm. Biotechnol., 2018, 19(4), 308-335.
[http://dx.doi.org/10.2174/1389201019666180620111025] [PMID: 29929461]
[3]
Georgieva, D.; Arni, R.K.; Betzel, C. Proteome analysis of snake venom toxins: pharmacological insights. Expert Rev. Proteomics, 2008, 5(6), 787-797.
[http://dx.doi.org/10.1586/14789450.5.6.787] [PMID: 19086859]
[4]
Schaloske, R.H.; Dennis, E.A. The phospholipase A2 superfamily and its group numbering system. Biochim. Biophys. Acta, 2006, 1761(11), 1246-1259.
[http://dx.doi.org/10.1016/j.bbalip.2006.07.011] [PMID: 16973413]
[5]
Dennis, E.A.; Cao, J.; Hsu, Y.H.; Magrioti, V.; Kokotos, G. Phospholipase A2 enzymes: Physical structure, biological function, disease implication, chemical inhibition, and therapeutic intervention. Chem. Rev., 2011, 111(10), 6130-6185.
[http://dx.doi.org/10.1021/cr200085w] [PMID: 21910409]
[6]
Gutiérrez, J.M.; Lomonte, B. Phospholipases A2: Unveiling the secrets of a functionally versatile group of snake venom toxins. Toxicon, 2013, 62, 27-39.
[http://dx.doi.org/10.1016/j.toxicon.2012.09.006] [PMID: 23025922]
[7]
Ponce-Soto, L.A.; Martins-de-Souza, D.; Marangoni, S. Neurotoxic, myotoxic and cytolytic activities of the new basic PLA(2) isoforms BmjeTX-I and BmjeTX-II isolated from the Bothrops marajoensis (Marajó Lancehead) snake venom. Protein J., 2010, 29(2), 103-113.
[http://dx.doi.org/10.1007/s10930-010-9229-5] [PMID: 20195718]
[8]
Gutiérrez, J.M.; Lomonte, B.; Gutiérrez, J.M.; Lomonte, B. Phospholipase A2 myotoxins from Bothrops snake venoms. Toxicon, 1995, 33(11), 1405-1424.
[http://dx.doi.org/10.1016/0041-0101(95)00085-Z] [PMID: 8744981]
[9]
Lomonte, B.; Angulo, Y.; Sasa, M.; Gutiérrez, J.M. The phospholipase A2 homologues of snake venoms: biological activities and their possible adaptive roles. Protein Pept. Lett., 2009, 16(8), 860-876.
[http://dx.doi.org/10.2174/092986609788923356] [PMID: 19689412]
[10]
Kini, R.M. Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes. Toxicon, 2003, 42(8), 827-840.
[http://dx.doi.org/10.1016/j.toxicon.2003.11.002] [PMID: 15019485]
[11]
Maraganore, J.M.; Merutka, G.; Cho, W.; Welches, W.; Kézdy, F.J.; Heinrikson, R.L. A new class of phospholipases A2 with lysine in place of aspartate 49. Functional consequences for calcium and substrate binding. J. Biol. Chem., 1984, 259(22), 13839-13843.
[PMID: 6438084]
[12]
Ownby, C.L.; Selistre de Araujo, H.S.; White, S.P.; Fletcher, J.E. Lysine 49 phospholipase A2 proteins. Toxicon, 1999, 37(3), 411-445.
[http://dx.doi.org/10.1016/S0041-0101(98)00188-3] [PMID: 10080349]
[13]
Lomonte, B.; Moreno, E.; Tarkowski, A.; Hanson, L.Å.; Maccarana, M. Neutralizing interaction between heparins and myotoxin II, a lysine 49 phospholipase A2 from Bothrops asper snake venom. Identification of a heparin-binding and cytolytic toxin region by the use of synthetic peptides and molecular modeling. J. Biol. Chem., 1994, 269(47), 29867-29873.
[PMID: 7961981]
[14]
Soares, A.M.; Guerra-Sá, R.; Borja-Oliveira, C.R.; Rodrigues, V.M.; Rodrigues-Simioni, L.; Rodrigues, V.; Fontes, M.R.; Lomonte, B.; Gutiérrez, J.M.; Giglio, J.R. Structural and functional characterization of BnSP-7, a Lys49 myotoxic phospholipase A(2) homologue from Bothrops neuwiedi pauloensis venom. Arch. Biochem. Biophys., 2000, 378(2), 201-209.
[http://dx.doi.org/10.1006/abbi.2000.1790] [PMID: 10860537]
[15]
Salvador, G.H.M.; Dos Santos, J.I.; Borges, R.J.; Fontes, M.R.M. Structural evidence for a fatty acid-independent myotoxic mechanism for a phospholipase A2-like toxin. Biochim. Biophys. Acta. Proteins Proteomics, 2018, 1866(3), 473-481.
[http://dx.doi.org/10.1016/j.bbapap.2017.12.008] [PMID: 29287778]
[16]
Nolte, S.; de Castro Damasio, D.; Baréa, A.C.; Gomes, J.; Magalhães, A.; Mello Zischler, L.F.C.; Stuelp-Campelo, P.M.; Elífio-Esposito, S.L.; Roque-Barreira, M.C.; Reis, C.A.; Moreno-Amaral, A.N. BJcuL, a lectin purified from Bothrops jararacussu venom, induces apoptosis in human gastric carcinoma cells accompanied by inhibition of cell adhesion and actin cytoskeleton disassembly. Toxicon, 2012, 59(1), 81-85.
[http://dx.doi.org/10.1016/j.toxicon.2011.10.012] [PMID: 22079298]
[17]
Rodrigues, R.S.; da Silva, J.F.; Boldrini França, J.; Fonseca, F.P.P.; Otaviano, A.R.; Henrique Silva, F.; Hamaguchi, A.; Magro, A.J.; Braz, A.S.; dos Santos, J.I.; Homsi-Brandeburgo, M.I.; Fontes, M.R.; Fuly, A.L.; Soares, A.M.; Rodrigues, V.M. Structural and functional properties of Bp-LAAO, a new L-amino acid oxidase isolated from Bothrops pauloensis snake venom. Biochimie, 2009, 91(4), 490-501.
[http://dx.doi.org/10.1016/j.biochi.2008.12.004] [PMID: 19135502]
[18]
Zouari-Kessentini, R.; Srairi-Abid, N.; Bazaa, A.; El Ayeb, M.; Luis, J.; Marrakchi, N. Antitumoral potential of Tunisian snake venoms secreted phospholipases A2. BioMed Res. Int., 2013, 2013391389
[http://dx.doi.org/10.1155/2013/391389] [PMID: 23509718]
[19]
Costa, T.R.; Menaldo, D.L.; Oliveira, C.Z.; Santos-Filho, N.A.; Teixeira, S.S.; Nomizo, A.; Fuly, A.L.; Monteiro, M.C.; de Souza, B.M.; Palma, M.S.; Stábeli, R.G.; Sampaio, S.V.; Soares, A.M. Myotoxic phospholipases A(2) isolated from Bothrops brazili snake venom and synthetic peptides derived from their C-terminal region: cytotoxic effect on microorganism and tumor cells. Peptides, 2008, 29(10), 1645-1656.
[http://dx.doi.org/10.1016/j.peptides.2008.05.021] [PMID: 18602430]
[20]
Cecilio, A.B.; Caldas, S.; Oliveira, R.A.; Santos, A.S.; Richardson, M.; Naumann, G.B.; Schneider, F.S.; Alvarenga, V.G.; Estevão-Costa, M.I.; Fuly, A.L.; Eble, J.A.; Sanchez, E.F. Molecular characterization of Lys49 and Asp49 phospholipases A2from snake venom and their antiviral activities against Dengue virus. Toxins (Basel), 2013, 5(10), 1780-1798.
[http://dx.doi.org/10.3390/toxins5101780] [PMID: 24131891]
[21]
Muller, V.D.; Soares, R.O.; dos Santos, N.N., Jr; Trabuco, A.C.; Cintra, A.C.; Figueiredo, L.T.; Caliri, A.; Sampaio, S.V.; Aquino, V.H. Phospholipase A2 isolated from the venom of Crotalus durissus terrificus inactivates dengue virus and other enveloped viruses by disrupting the viral envelope. PLoS One, 2014, 9(11)e112351
[http://dx.doi.org/10.1371/journal.pone.0112351] [PMID: 25383618]
[22]
Rodrigues, V.M.; Marcussi, S.; Cambraia, R.S.; de Araújo, A.L.; Malta-Neto, N.R.; Hamaguchi, A.; Ferro, E.A.; Homsi-Brandeburgo, M.I.; Giglio, J.R.; Soares, A.M. Bactericidal and neurotoxic activities of two myotoxic phospholipases A2 from Bothrops neuwiedi pauloensis snake venom. Toxicon, 2004, 44(3), 305-314.
[http://dx.doi.org/10.1016/j.toxicon.2004.06.008] [PMID: 15302537]
[23]
Páramo, L.; Lomonte, B.; Pizarro-Cerdá, J.; Bengoechea, J.A.; Gorvel, J.P.; Moreno, E. Bactericidal activity of Lys49 and Asp49 myotoxic phospholipases A2 from Bothrops asper snake venom--synthetic Lys49 myotoxin II-(115-129)-peptide identifies its bactericidal region. Eur. J. Biochem., 1998, 253(2), 452-461.
[http://dx.doi.org/10.1046/j.1432-1327.1998.2530452.x] [PMID: 9654096]
[24]
Costa Torres, A.F.; Dantas, R.T.; Toyama, M.H.; Diz Filho, E.; Zara, F.J.; Rodrigues de Queiroz, M.G.; Pinto Nogueira, N.A.; Rosa de Oliveira, M.; de Oliveira Toyama, D.; Monteiro, H.S.; Martins, A.M. Antibacterial and antiparasitic effects of Bothrops marajoensis venom and its fractions: Phospholipase A2 and L-amino acid oxidase. Toxicon, 2010, 55(4), 795-804.
[http://dx.doi.org/10.1016/j.toxicon.2009.11.013] [PMID: 19944711]
[25]
Nunes, D.C.; Figueira, M.M.; Lopes, D.S.; De Souza, D.L.; Izidoro, L.F.; Ferro, E.A.; Souza, M.A.; Rodrigues, R.S.; Rodrigues, V.M.; Yoneyama, K.A. BnSP-7 toxin, a basic phospholipase A2 from Bothrops pauloensis snake venom, interferes with proliferation, ultrastructure and infectivity of Leishmania (Leishmania) amazonensis. Parasitology, 2013, 140(7), 844-854.
[http://dx.doi.org/10.1017/S0031182013000012] [PMID: 23442579]
[26]
Sobrinho, J.C.; Simões-Silva, R.; Holanda, R.J.; Alfonso, J.; Gomez, A.F.; Zanchi, F.B.; Moreira-Dill, L.S.; Grabner, A.N.; Zuliani, J.P.; Calderon, L.A.; Soares, A.M.; Soares, A.M. Antitumoral potential of snake venom Phospholipases A2 and synthetic peptides. Curr. Pharm. Biotechnol., 2016, 17(14), 1201-1212.
[http://dx.doi.org/10.2174/1389201017666160808154250] [PMID: 27604356]
[27]
Prinholato da Silva, C.; Costa, T.R.; Paiva, R.M.A.; Cintra, A.C.O.; Menaldo, D.L.; Antunes, L.M.G.; Sampaio, S.V. Antitumor potential of the myotoxin BthTX-I from Bothrops jararacussu snake venom: evaluation of cell cycle alterations and death mechanisms induced in tumor cell lines. J. Venom. Anim. Toxins Incl. Trop. Dis., 2015, 21(1), 44.
[http://dx.doi.org/10.1186/s40409-015-0044-5] [PMID: 26539212]
[28]
Laemmli, U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature, 1970, 227(5259), 680-685.
[http://dx.doi.org/10.1038/227680a0] [PMID: 5432063]
[29]
Edman, P.; Högfeldt, E.; Sillén, L.G.; Kinell, P-O. Method for determination of the amino acid sequence in peptides. Acta Chem. Scand., 1950, 4, 283-293.
[http://dx.doi.org/10.3891/acta.chem.scand.04-0283]
[30]
Vega, C.; Rolón, M.; Martínez-Fernández, A.R.; Escario, J.A.; Gómez-Barrio, A. A new pharmacological screening assay with Trypanosoma cruzi epimastigotes expressing β-galactosidase. Parasitol. Res., 2005, 95(4), 296-298.
[http://dx.doi.org/10.1007/s00436-005-1300-3] [PMID: 15682334]
[31]
Rolón, M.; Vega, C.; Escario, J.A.; Gómez-Barrio, A. Development of resazurin microtiter assay for drug sensibility testing of Trypanosoma cruzi epimastigotes. Parasitol. Res., 2006, 99(2), 103-107.
[http://dx.doi.org/10.1007/s00436-006-0126-y] [PMID: 16506080]
[32]
Angulo, Y.; Lomonte, B. Biochemistry and toxicology of toxins purified from the venom of the snake Bothrops asper. Toxicon, 2009, 54(7), 949-957.
[http://dx.doi.org/10.1016/j.toxicon.2008.12.014] [PMID: 19111755]
[33]
Calvete, J.J.; Juárez, P.; Sanz, L. Snake venomics. Strategy and applications. J. Mass Spectrom., 2007, 42(11), 1405-1414.
[http://dx.doi.org/10.1002/jms.1242] [PMID: 17621391]
[34]
Stabeli, R.G.; Simoes-Silva, R.; Kayano, A.M.; Gimenez, G.S.; Moura, A. Purification of Phospholipases A2 from American snake venoms. Chromatography - The Most Versatile Method of Chemical Analysis; InTech, 2012, pp. 1-34.
[35]
Soares, A.M.; Rodrigues, V.M.; Homsi-Brandeburgo, M.I.; Toyama, M.H.; Lombardi, F.R.; Arni, R.K.; Giglio, J.R. A rapid procedure for the isolation of the Lys-49 myotoxin II from Bothrops moojeni (caissaca) venom: Biochemical characterization, crystallization, myotoxic and edematogenic activity. Toxicon, 1998, 36(3), 503-514.
[http://dx.doi.org/10.1016/S0041-0101(97)00133-5] [PMID: 9637370]
[36]
Andrião-Escarso, S.H.; Soares, A.M.; Rodrigues, V.M.; Angulo, Y.; Díaz, C.; Lomonte, B.; Gutiérrez, J.M.; Giglio, J.R. Myotoxic phospholipases A(2) in bothrops snake venoms: effect of chemical modifications on the enzymatic and pharmacological properties of bothropstoxins from Bothrops jararacussu. Biochimie, 2000, 82(8), 755-763.
[http://dx.doi.org/10.1016/S0300-9084(00)01150-0] [PMID: 11018293]
[37]
Núñez, V.; Arce, V.; Gutiérrez, J.M.; Lomonte, B. Structural and functional characterization of myotoxin I, a Lys49 phospholipase A2 homologue from the venom of the snake Bothrops atrox. Toxicon, 2004, 44(1), 91-101.
[http://dx.doi.org/10.1016/j.toxicon.2004.04.013] [PMID: 15225567]
[38]
Corrêa, E.A.; Kayano, A.M.; Diniz-Sousa, R.; Setúbal, S.S.; Zanchi, F.B.; Zuliani, J.P.; Matos, N.B.; Almeida, J.R.; Resende, L.M.; Marangoni, S.; da Silva, S.L.; Soares, A.M.; Calderon, L.A. Isolation, structural and functional characterization of a new Lys49 phospholipase A2 homologue from Bothrops neuwiedi urutu with bactericidal potential. Toxicon, 2016, 115, 13-21.
[http://dx.doi.org/10.1016/j.toxicon.2016.02.021] [PMID: 26927324]
[39]
Teixera, L.F.; de Carvalho, L.H.; de Castro, O.B.; Bastos, J.S.F.; Néry, N.M.; Oliveira, G.A.; Kayano, A.M.; Soares, A.M.; Zuliani, J.P. Local and systemic effects of BdipTX-I, a Lys-49 phospholipase A2 isolated from Bothrops diporus snake venom. Toxicon, 2018, 141, 55-64.
[http://dx.doi.org/10.1016/j.toxicon.2017.11.007] [PMID: 29170054]
[40]
de Moura, A.A.; Kayano, A.M.; Oliveira, G.A.; Setúbal, S.S.; Ribeiro, J.G.; Barros, N.B.; Nicolete, R.; Moura, L.A.; Fuly, A.L.; Nomizo, A.; da Silva, S.L.; Fernandes, C.F.; Zuliani, J.P.; Stábeli, R.G.; Soares, A.M.; Calderon, L.A. Purification and biochemical characterization of three myotoxins from Bothrops mattogrossensis snake venom with toxicity against Leishmania and tumor cells. BioMed Res. Int., 2014, 2014195356
[http://dx.doi.org/10.1155/2014/195356] [PMID: 24724078]
[41]
Lomonte, B. Rangel, J. Snake venom Lys49 myotoxins: From phospholipases A(2) to non-enzymatic membrane disruptors. Toxicon, 2012, 60(4), 520-530.
[http://dx.doi.org/10.1016/j.toxicon.2012.02.007] [PMID: 22781132]
[42]
Calvete, J.J. Venomics: integrative venom proteomics and beyond. Biochem. J., 2017, 474(5), 611-634.
[http://dx.doi.org/10.1042/BCJ20160577] [PMID: 28219972]
[43]
Calvete, J. J. Snake venomics: from the inventory of toxins to biology. Toxicon, 2013, 75, 44-62.
[http://dx.doi.org/10.1016/j.toxicon.2013.03.020] [PMID: 23578513]
[44]
Saravia, P.; Rojas, E.; Arce, V.; Guevara, C.; López, J.C.; Chaves, E.; Velásquez, R.; Rojas, G.; Gutiérrez, J.M. Geographic and ontogenic variability in the venom of the neotropical rattlesnake Crotalus durissus: pathophysiological and therapeutic implications. Rev. Biol. Trop., 2002, 50(1), 337-346.
[PMID: 12298262]
[45]
Alape-Girón, A.; Sanz, L.; Escolano, J.; Flores-Díaz, M.; Madrigal, M.; Sasa, M.; Calvete, J.J. Snake venomics of the lancehead pitviper Bothrops asper: geographic, individual, and ontogenetic variations. J. Proteome Res., 2008, 7(8), 3556-3571.
[http://dx.doi.org/10.1021/pr800332p] [PMID: 18557640]
[46]
Renetseder, R.; Brunie, S.; Dijkstra, B.W.; Drenth, J.; Sigler, P.B. A comparison of the crystal structures of phospholipase A2 from bovine pancreas and Crotalus atrox venom. J. Biol. Chem., 1985, 260(21), 11627-11634.
[PMID: 4044572]
[47]
Angulo, Y.; Olamendi-Portugal, T.; Alape-Girón, A.; Possani, L.D.; Lomonte, B. Structural characterization and phylogenetic relationships of myotoxin II from Atropoides (Bothrops) nummifer snake venom, a Lys49 phospholipase A(2) homologue. Int. J. Biochem. Cell Biol., 2002, 34(10), 1268-1278.
[http://dx.doi.org/10.1016/S1357-2725(02)00060-2] [PMID: 12127577]
[48]
Stábeli, R.G.; Amui, S.F.; Sant’Ana, C.D.; Pires, M.G.; Nomizo, A.; Monteiro, M.C.; Romão, P.R.; Guerra-Sá, R.; Vieira, C.A.; Giglio, J.R.; Fontes, M.R.; Soares, A.M. Bothrops moojeni myotoxin-II, a Lys49-phospholipase A2 homologue: an example of function versatility of snake venom proteins. Comp. Biochem. Physiol. C Toxicol. Pharmacol., 2006, 142(3-4), 371-381.
[http://dx.doi.org/10.1016/j.cbpc.2005.11.020] [PMID: 16442348]
[49]
King, G. Venoms to drugs: Translating venom peptides into therapeutics. Aust. Biochem., 2013, 44, 13-16.
[50]
Harvey, A.L.; Edrada-Ebel, R.; Quinn, R.J. The re-emergence of natural products for drug discovery in the genomics era. Nat. Rev. Drug Discov., 2015, 14(2), 111-129.
[http://dx.doi.org/10.1038/nrd4510] [PMID: 25614221]
[51]
Koh, D.C.; Armugam, A.; Jeyaseelan, K. Snake venom components and their applications in biomedicine. Cell. Mol. Life Sci., 2006, 63(24), 3030-3041.
[http://dx.doi.org/10.1007/s00018-006-6315-0] [PMID: 17103111]
[52]
Earl, S.T.H.; Masci, P.P.; de Jersey, J.; Lavin, M.F.; Dixon, J. Drug development from Australian elapid snake venoms and the Venomics pipeline of candidates for haemostasis: Textilinin-1 (Q8008), Haempatch™ (Q8009) and CoVase™ (V0801). Toxicon, 2012, 59(4), 456-463.
[http://dx.doi.org/10.1016/j.toxicon.2010.12.010] [PMID: 21184772]
[53]
Koh, C.Y.; Kini, R.M. From snake venom toxins to therapeutics--cardiovascular examples. Toxicon, 2012, 59(4), 497-506.
[http://dx.doi.org/10.1016/j.toxicon.2011.03.017] [PMID: 21447352]
[54]
Castillo, J.C.; Vargas, L.J.; Segura, C.; Gutiérrez, J.M.; Pérez, J.C. In vitro antiplasmodial activity of phospholipases A2 and a phospholipase homologue isolated from the venom of the snake Bothrops asper. Toxins (Basel), 2012, 4(12), 1500-1516.
[http://dx.doi.org/10.3390/toxins4121500] [PMID: 23242318]
[55]
Passero, L.F.D.; Laurenti, M.D.; Tomokane, T.Y.; Corbett, C.E.P.; Toyama, M.H. The effect of phospholipase A2 from Crotalus durissus collilineatus on Leishmania (Leishmania) amazonensis infection. Parasitol. Res., 2008, 102(5), 1025-1033.
[http://dx.doi.org/10.1007/s00436-007-0871-6] [PMID: 18180953]
[56]
Castillo-Vigil, A.; Randall, L.; Zeledón, R.; Lomonte, B.; Urbina, A.; Valverde, B. Susceptibilidad de Trypanosoma cruzi a diferentes venenos de serpientes de Costa Rica. Bol. Malariol. Salud Ambient., 2008, XLVIII(2), 135-144.
[57]
Deolindo, P.; Teixeira-Ferreira, A.S.; Melo, E.J.; Arnholdt, A.C.; Souza, Wd.; Alves, E.W.; DaMatta, R.A. Programmed cell death in Trypanosoma cruzi induced by Bothrops jararaca venom. Mem. Inst. Oswaldo Cruz, 2005, 100(1), 33-38.
[http://dx.doi.org/10.1590/S0074-02762005000100006] [PMID: 15867960]
[58]
Deolindo, P.; Teixeira-Ferreira, A.S.; DaMatta, R.A.; Alves, E.W. L-amino acid oxidase activity present in fractions of Bothrops jararaca venom is responsible for the induction of programmed cell death in Trypanosoma cruzi. Toxicon, 2010, 56(6), 944-955.
[http://dx.doi.org/10.1016/j.toxicon.2010.06.019] [PMID: 20615423]
[59]
Adade, C.M.; Carvalho, A.L.O.; Tomaz, M.A.; Costa, T.F.R.; Godinho, J.L.; Melo, P.A.; Lima, A.P.C.A.; Rodrigues, J.C.F.; Zingali, R.B.; Souto-Padrón, T. Crovirin, a snake venom cysteine-rich secretory protein (CRISP) with promising activity against Trypanosomes and Leishmania. PLoS Negl. Trop. Dis., 2014, 8(10)e3252
[http://dx.doi.org/10.1371/journal.pntd.0003252] [PMID: 25330220]
[60]
Adade, C.M.; Cons, B.L.; Melo, P.A.; Souto-Padrón, T. Effect of Crotalus viridis viridis snake venom on the ultrastructure and intracellular survival of Trypanosoma cruzi. Parasitology, 2011, 138(1), 46-58.
[http://dx.doi.org/10.1017/S0031182010000958] [PMID: 20663246]
[61]
Gonçalves, A.R.; Soares, M.J.; de Souza, W.; DaMatta, R.A.; Alves, E.W. Ultrastructural alterations and growth inhibition of Trypanosoma cruzi and Leishmania major induced by Bothrops jararaca venom. Parasitol. Res., 2002, 88(7), 598-602.
[http://dx.doi.org/10.1007/s00436-002-0626-3] [PMID: 12107450]
[62]
Grabner, A.N.; Alfonso, J.; Kayano, A.M.; Moreira-Dill, L.S.; Dos Santos, A.P.A.; Caldeira, C.A.S.; Sobrinho, J.C.; Gómez, A.; Grabner, F.P.; Cardoso, F.F.; Zuliani, J.P.; Fontes, M.R.M.; Pimenta, D.C.; Gómez, C.V.; Teles, C.B.G.; Soares, A.M.; Calderon, L.A. BmajPLA2-II, a basic Lys49-phospholipase A2 homologue from Bothrops marajoensis snake venom with parasiticidal potential. Int. J. Biol. Macromol., 2017, 102, 571-581.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.04.013] [PMID: 28390830]
[63]
Sobrinho, J.C.; Kayano, A.M.; Simões-Silva, R.; Alfonso, J.J.; Gomez, A.F.; Gomez, M.C.; Zanchi, F.B.; Moura, L.A.; Souza, V.R.; Fuly, A.L.; de Oliveira, E.; da Silva, S.L.; Almeida, J.R.; Zuliana, J.P.; Soares, A.M. Anti-platelet aggregation activity of two novel acidic Asp49-Phospholipases A2 from Bothrops brazili snake venom. Int. J. Biol. Macromol., 2018, 107, 1014-1022.
[http://dx.doi.org/10.1016/j.ijbiomac.2017.09.069]
[64]
Mora-Obando, D.; Fernández, J.; Montecucco, C.; Gutiérrez, J.M.; Lomonte, B. Synergism between basic Asp49 and Lys49 phospholipase A2 myotoxins of viperid snake venom in vitro and in vivo. PLoS One, 2014, 9(10)e109846
[http://dx.doi.org/10.1371/journal.pone.0109846] [PMID: 25290688]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 19
ISSUE: 22
Year: 2019
Page: [2041 - 2048]
Pages: 8
DOI: 10.2174/1568026619666190723154756
Price: $65

Article Metrics

PDF: 20
HTML: 4