Oligosaccharide residues of Loxosceles intermedia (brown spider) venom proteins: dependence on glycosylation for dermonecrotic activity

Oligosaccharide residues of Loxosceles intermedia (brown spider) venom proteins: dependence on glycosylation for dermonecrotic activity

Autor Veiga, S. S. Google Scholar
Gremski, W. Google Scholar
Santos, VLP dos Google Scholar
Feitosa, L. Google Scholar
Mangili, O. C. Google Scholar
Nader, H. B. Google Scholar
Dietrich, C. P. Google Scholar
Brentani, R. R. Google Scholar
Instituição Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Ludwig Inst Canc Res
Resumo Loxosceles spp. (brown spider) envenomation has been reported to provoke dermonecrosis and haemorrhage at the bite site (a hallmark of accidents) and, to a lesser extent, thrombocytopenia, hemolysis and disseminated intravascular coagulation in some cases. Using lectin-immunolabeling, lectin-affinity chromatography, glycosidase and proteinase K treatments we were able to identify several venom N-glycosylated proteins with high-mannose oligosaccharide structures, complex-type glycoconjugates such as fucosylated glycans, but no galactose or sialic acid residues as complex sugars or glycosaminoglycan residues. Working with enzymatically or chemically deglycosylated venom we found that platelet aggregation (thrombocytopenic activity) as well as the fibronectinolytic and fibrinogenolytic (haemorrhagic) effects of the venom were sugar-independent when compared to glycosylated venom. Nevertheless, zymograph analysis in co-polymerized gelatin gels showed that enzymatic N-deglycosylation of loxolysin-B, a high mannose 32-35 kDa glycoprotein of the venom with gelatinolytic metalloproteinase activity, caused a reduction of approximately 2 kDa in its molecular weight and a reduction of the gelatinolytic effect to a residual activity of 28% when compared to the glycosylated molecule. indicating a post-translational glycosylation-dependent gelatinolytic effect. Analysis of the dermonecrotic effect of the chemically or enzymatically N-deglycosylated venom detected only residual activity when compared with the glycosylated control. Thus, the present report suggests that oligosaccharide moieties play a role in the destructive effects of brown spider venom and opens the possibility for a carbohydrate-based therapy. (C) 1999 Elsevier B.V. All rights reserved.
Idioma Inglês
Data de publicação 1999-04-01
Publicado em Toxicon. Oxford: Pergamon-Elsevier B.V., v. 37, n. 4, p. 587-607, 1999.
ISSN 0041-0101 (Sherpa/Romeo, fator de impacto)
Publicador Elsevier B.V.
Extensão 587-607
Fonte http://dx.doi.org/10.1016/S0041-0101(98)00198-6
Direito de acesso Acesso restrito
Tipo Artigo
Web of Science WOS:000078642100002
Endereço permanente http://repositorio.unifesp.br/handle/11600/26057

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