Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity

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dc.contributor.author Kusma, J.
dc.contributor.author Chaim, O. M. [UNIFESP]
dc.contributor.author Wille, A. C. M.
dc.contributor.author Ferrer, V. P.
dc.contributor.author Sade, Y. B.
dc.contributor.author Donatti, L.
dc.contributor.author Gremski, W.
dc.contributor.author Mangili, O. C.
dc.contributor.author Veiga, S. S.
dc.date.accessioned 2016-01-24T13:51:51Z
dc.date.available 2016-01-24T13:51:51Z
dc.date.issued 2008-11-01
dc.identifier http://dx.doi.org/10.1016/j.biochi.2008.07.011
dc.identifier.citation Biochimie. Paris: Elsevier France-editions Scientifiques Medicales Elsevier, v. 90, n. 11-12, p. 1722-1736, 2008.
dc.identifier.issn 0300-9084
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/31002
dc.description.abstract Bites from brown spiders (Loxosceles genus) have clinical manifestations including skin necrosis with gravitational spreading, and systemic involvement that may include renal failure, hemolysis, and thrombocytopenia. Mice were exposed to recombinant wild-type phospholipase-D, or to an isoform with a mutation in the catalytic domain resulting in no phospholipasic activity. Renal biopsies from mice treated with the wild-type toxin showed glomerular edema, erythrocytes and collapse of Bowman's space, edema and deposition of proteinaceous material within the tubular lumen. Ultrastructural analyses confirmed cytotoxicity by demonstrating disorders of glomerulus at foot processes and at fenestrated endothelium. Tubule alterations include deposits of amorphous material and edema, as well as an increase of epithelial cytoplasmic multi-vesicular bodies and electron-dense structures. There was an absence of nephrotoxicity in mice treated with the mutated toxin. Analyses of urine and blood showed that wild type toxin induced hematuria and elevation of blood urea, while treatment with mutated toxin caused no changes. Mouse lethality experiments also showed oliguria and mortality after treatment with wild-type toxin, but not following exposure to the mutated toxin. Immunofluorescence using antibodies to phospholipase-D toxin showed deposition of both toxins along the renal tubular structures as detected by confocal microscopy. Immunoblots of urine showed a 30 kDa band in samples from animals treated with wild-type toxin, but no band from mice exposed to mutated toxin. Wild-type toxin treatment caused cytoplasmic vacuolization, impaired spreading, reduction of cellular viability, and cell-cell and cell-substratum detachment in MDCK cells, while treatment with mutated isoform had no effect. Finally, there is a direct correlation between toxin activity on cell membrane phospholipids generating choline and cytotoxicity. We have defined for the first time a molecular mechanism for Loxosceles venom nephrotoxicity that is dependent on the catalytic activity of phospholipase-D toxin. (c) 2008 Elsevier Masson SAS. All rights reserved. en
dc.description.sponsorship Secretaria de Estado de Ciencia
dc.description.sponsorship Tecnologia e Ensino Superior (SETI) do Parana
dc.description.sponsorship Fundacao Araucaria-PR
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.format.extent 1722-1736
dc.language.iso eng
dc.publisher Elsevier B.V.
dc.relation.ispartof Biochimie
dc.rights Acesso restrito
dc.subject Brown spider en
dc.subject Venom en
dc.subject Phospholipase-D en
dc.subject Nephrotoxicity en
dc.title Nephrotoxicity caused by brown spider venom phospholipase-D (dermonecrotic toxin) depends on catalytic activity en
dc.type Artigo
dc.rights.license http://www.elsevier.com/about/open-access/open-access-policies/article-posting-policy
dc.contributor.institution Univ Fed Parana
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Univ Estadual Ponta Grossa
dc.contributor.institution Catholic Univ Parana
dc.description.affiliation Univ Fed Parana, Dept Cell Biol, BR-81531990 Curitiba, Parana, Brazil
dc.description.affiliation Universidade Federal de São Paulo, Dept Biochem, São Paulo, Brazil
dc.description.affiliation Univ Estadual Ponta Grossa, Dept Struct Mol Biol & Genet, Ponta Grossa, Parana, Brazil
dc.description.affiliation Catholic Univ Parana, Hlth & Biol Sci Inst, Curitiba, Parana, Brazil
dc.description.affiliation Univ Fed Parana, Dept Physiol, BR-81531990 Curitiba, Parana, Brazil
dc.description.affiliationUnifesp Universidade Federal de São Paulo, Dept Biochem, São Paulo, Brazil
dc.identifier.doi 10.1016/j.biochi.2008.07.011
dc.description.source Web of Science
dc.identifier.wos WOS:000261567400013



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