Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/101737
Type: Artigo de periódico
Title: Mn2+ Ions Reduce The Enzymatic And Pharmacological Activities Of Bothropstoxin-i, A Myotoxic Lys49 Phospholipase A2 Homologue From Bothrops Jararacussu Snake Venom
Author: Soares A.M.
Oshima-Franco Y.
Vieira C.A.
Leite G.B.
Fletcher J.E.
Jiang M.-S.
Cintra A.C.O.
Giglio J.R.
Rodrigues-Simioni L.
Abstract: Bothropstoxin-I (BthTX-I), a myotoxic Lys49 phospholipase A2 (PLA2) homologue isolated from Bothrops jararacussu snake venom, causes a range of biological effects, including myonecrosis, mouse paw edema, irreversible neuromuscular blockade and lysis of cell cultures. Among eight divalent cations assayed, Mn2+ was the most effective in reducing mouse paw edema induced by BthTX-I (25μg). Preincubating BthTX-I with Mn2+ (1.0mM) reduced mouse paw edema by 70% and myotoxicity by 60% in mice injected i.m. with 50μg toxin. Mn2+ (50μl of a 1mM solution) administered within 1min at the site of toxin injection was still but less effective in antagonising BthTX-I-induced myotoxicity. Mn2+ (1.0mM) completely prevented BthTX-I (1.4μM)-induced neuromuscular blockade in the mouse phrenic-nerve diaphragm preparation. Mn2+ (0.25mM) protected about 85% of NB41A3 cells from lysis when coincubated with BthTX-I (1.0μM) for 25h. Preincubation with 0.25mM Mn2+ increased the sensitivity of the cells to subsequent lysis by BthTX-I in the absence of Mn2+. BthTX-I (1μM) caused extensive fatty acid release (from 0.8% of the total radiolabeled lipid in control cells to 56% with toxin) when incubated with the NB41A3 cell line for 25h. PLA2 activity observed in cell cultures after addition of BthTX-I was considerably reduced by 0.25mM Mn2+. Mn2+ ions constitute a promising agent to assess the action mechanism and the effects of enzymatic inhibition on the pharmacological activity of Lys49 PLA2 homologues. © 2002 Elsevier Science Ltd. All rights reserved.
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Rights: fechado
Identifier DOI: 10.1016/S1357-2725(01)00174-1
Address: http://www.scopus.com/inward/record.url?eid=2-s2.0-0036217615&partnerID=40&md5=05765bb0775e9a22f79b23a32c3d0c48
Date Issue: 2002
Appears in Collections:Unicamp - Artigos e Outros Documentos

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