Artículos de revistas
Functional Characterization Of A Basic D49 Phospholipase A2 (lmtx-i) From The Venom Of The Snake Lachesis Muta Muta (bushmaster)
Registro en:
Toxicon. , v. 47, n. 7, p. 759 - 765, 2006.
410101
10.1016/j.toxicon.2006.02.007
2-s2.0-33646782230
Autor
Damico D.C.S.
Bueno L.G.F.
Rodrigues-Simioni L.
Marangoni S.
da Cruz-Hofling M.A.
Novello J.C.
Institución
Resumen
The whole venom of Lachesis muta muta is preponderantly neurotoxic but moderately myotoxic on the chick biventer cervicis preparation (BCp). We have now examined these toxic activities of a basic phospholipase A2, LmTX-I, isolated from the whole venom. LmTX-I caused a significant concentration-dependent neuromuscular blockade in the BCp. The time to produce 50% neuromuscular blockade was 14.7±0.75 min (30 μg/ml), 23.6±0.9 min (10 μg/ml), 34±1.7 min (2.5 μg/ml) and 39.2±3.6 min (1 μg/ml), (n=5/concentration; p<0.05). Complete blockade with all tested concentrations was not accompanied by inhibition of the response to ACh. At the highest concentration, LmTX-I (30 μg/ml) significantly reduced contractures elicited by exogenous KCl (20 mM), increased the release of creatine kinase (1542.5±183.9 IU/L vs 442.7±39.8 IU/L for controls after 120 min, p<0.05), and induced the appearance of degenerating muscle fibers (∼15%). Quantification of myonecrosis indicated 14.8±0.8 and 2.0±0.4%, with 30 and 10 μg/ml venom concentration, respectively, against 1.07±0.4% for control preparations. The findings indicate that the basic PLA2 present on venom from L. m. muta (LmTX-I) possesses a dominant neurotoxic action on isolated chick nerve-muscle preparations, whereas myotoxicity was mainly observed at the highest concentration used (30 μg/ml). These effects of LmTX-I closely reproduce the effects of the whole venom of L. m. muta in chick neuromuscular preparations. © 2006 Elsevier Ltd. All rights reserved. 47 7 759 765 Beghini, D.G., Toyama, M.H., Hyslop, S., Sodek, L.C., Novello, J.C., Marangoni, S., Enzymatic characterization of a novel phospholipase A2 from Crotalus durissus cascavella rattlesnake (maracambóia) venom (2000) J. Protein Chem., 19, pp. 679-684 Cho, W., Kezdy, F.J., Chromogenic substrates and assay of phospholipases A2 (1991) Meth. Enzymol., 197, pp. 75-79 Damico, D.C.S., Bueno, L.G.F., Rodrigues-Simioni, L., Marangoni, S., Cruz-Höfling, M.A., Novello, J.C., Neurotoxic and myotoxic actions from Lachesis muta muta (surucucu) whole venom on the mouse and chick nerve-muscle preparations (2005) Toxicon, 46, pp. 222-229 Damico, D.C.S., Lilla, S., de Nucci, G., Ponce-Soto, L.A., Winck, F.V., Novello, J.C., Marangoni, S., Biochemical and Enzymatic characterization of two basic Asp49 Phospholipase A2 isoforms from Lachesis muta muta (Surucucu) venom (2005) Biochim. Biophys. Acta, 1726, pp. 75-86 Diniz, M.R., Oliveira, E.B., Purification and properties of a Kininogenin from the venom of Lachesis muta (bushmaster) (1992) Toxicon, 30, pp. 247-258 Estêvão-Costa, M.I., Diniz, C.R., Magalhães, A., Markland, F.S., Sanchez, E.F., Action of metalloproteinases mutalysin I and II on several components of the hemostatic and fibrinolytic systems (2000) Thromb. Res., 99, pp. 363-376 Ginsborg, B.L., Warriner, J., The isolated chick biventer cervicis nerve muscle preparations (1960) Br. J. Pharmacol., 15, pp. 410-411 Gutiérrez, J.M., Rucavado, A., Escalante, T., Díaz, C., Hemorrhage induced by snake venom metalloproteinases: biochemical and biophysical mechanisms involved in microvessel damage (2005) Toxicon, 45, pp. 997-1011 Halpert, J., Eaker, D., Amino acid sequence of a presynaptic neurotoxin from the venom of Notechis scutatus scutatus (Australian tiger snake) (1975) J. Biol. Chem., 250, pp. 6990-6997 Harris, J.B., Vater, R., Wilson, M., Cullen, M.J., Muscle fibre breakdown in venom-induced muscle degeneration (2003) J. Anat., 202, pp. 363-372 Holzer, M., Mackessy, S.P., An aqueous endpoint assay of snake venom phospholipase A2 (1996) Toxicon, 34, pp. 1149-1155 Jorge, M.T., Sano-Martins, I.S., Tomy, S.C., Castro, S.C.B., Ferrari, R.A., Ribeiro, L.A., Warrell, D.A., Snakebite by the bushmaster (Lachesis muta) in Brazil: case report and review of the literature (1997) Toxicon, 35, pp. 545-554 Kini, R.M., Excitement ahead: structure, function and mechanism of snake venom phospholipase A2 enzymes (2003) Toxicon, 42, pp. 827-840 Kondo, K., Zhang, J., Xu, K., Kagamiyama, H., Amino acid sequence of a presynaptic neurotoxin, agkistrodotoxin, from the venom of Agkistrodon halys pallas (1989) J. Biochem. (Tokyo), 105, pp. 196-203 Laemmli, U.K., Cleavage of structural proteins during the assembly of the bacteriophage T4 (1970) Nature, 227, pp. 680-685 Ritonja, A., Gubensek, F., Ammoditoxin A, a highly lethal phospholipase A2 from Vipera ammodytes ammodytes venom (1985) Biochim. Biophys. Acta, 828, pp. 306-312 Viljoen, C.C., Botes, D.P., Kruger, H., Isolation and amino acid sequence of caudoxin, a presynaptic acting toxic phospholipase A2 from the venom of the horned puff adder (Bitis caudalis) (1982) Toxicon, 20, pp. 715-737