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Title: Cytotoxic, thrombolytic and edematogenic activities of leucurolysin-a, a metalloproteinase from Bothrops leucurus snake venom
Authors: Gremski, L. H.
Chaim, O. M.
Paludo, K. S.
Sade, Y. B.
Otuki, M. F.
Richardson, M.
Gremski, W.
Sanchez, E. F.
Veiga, S. S.
Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Esequiel Dias Fdn
Catholic Univ Parana
Keywords: Bothrops leucurus
Issue Date: 1-Jul-2007
Publisher: Elsevier B.V.
Citation: Toxicon. Oxford: Pergamon-Elsevier B.V., v. 50, n. 1, p. 120-134, 2007.
Abstract: Leucurolysin-a (leuc-a), a 23 kDa non-hemorrhagic metalloproteinase, is found in venom of the viper Bothrops leucurus. Here, we examine the biological consequences of leuc-a, including thrombolytic activity, direct effects on endothelial cells in culture and edematogenic activity in vivo. We demonstrate fibrinolytic activity of leuc-a, in which the protease specifically degrades alpha, beta, and gamma-gamma chains. While not causing hemorrhaging, leuc-a does cause thrombolytic activities in whole blood clots. Endothelial cells are highly resistant to leuc-a in culture. Cell viability suffered only when cells were exposed to large quantities of the protease. Nevertheless, leuc-a induces changes in cell morphology. the impact of leuc-a on cell adhesion was confirmed by an adhesion assay, in which cell adhesion to fibronectin decreased due to leuc-a. This mild cellular impact is unlike that of crude venom, where lower concentrations triggered cell death and a greater reduction in cell adhesion. Also, leuc-a increased microvessel permeability with marked edema in mice peritoneum and foot pads. These effects are similar to those of other P-I class SVPMs. These in vivo effects were weaker when crude venom was tested. in conclusion, albeit not showing significant hemorrhagic activity, leuc-a can induce a prominent edema which appears to be significant in the local effects observed after B. leucurus venom accidents. (c) 2007 Elsevier B.V. All rights reserved.
ISSN: 0041-0101
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