Identification, cloning and functional characterization of a novel dermonecrotic toxin (phospholipase D) from brown spider (Loxosceles intermedia) venom

Identification, cloning and functional characterization of a novel dermonecrotic toxin (phospholipase D) from brown spider (Loxosceles intermedia) venom

Author Appel, Marcia Helena Google Scholar
Silveira, Rafael Bertoni da Autor UNIFESP Google Scholar
Chaim, Olga Meiri Autor UNIFESP Google Scholar
Paludo, Katia Sabrina Google Scholar
Silva, Dilza Trevisan Google Scholar
Chaves, Daniele M. Google Scholar
Silva, Paulo Henrique da Google Scholar
Mangili, Oldernir C. Google Scholar
Senff-Ribeiro, Andrea Google Scholar
Gremski, Waldemiro Google Scholar
Nader, Helena B. Autor UNIFESP Google Scholar
Veiga, Silvio Sanches Google Scholar
Institution Univ Fed Parana
Universidade Federal de São Paulo (UNIFESP)
Catholic Univ
Abstract Brown spider bites are associated with lesions including dermonecrosis, gravitational spreading and a massive inflammatory response, along with systemic problems that may include hematological disturbances and renal failure. the mechanisms by which the venom exerts its noxious effects are currently under investigation. It is known that the venom contains a major toxin (dermonecrotic toxin, biochemically a phospholipase D) that can experimentally induce dermonecrosis, inflammatory response, animal mortality and platelet aggregation. Herein, we describe cloning, heterologous expression, purification and functionality of a novel isoform of the 33 kDa dermonecrotic toxin. Circular dichroism analysis evidenced correct folding for the toxin. the recombinant toxin was recognized by whole venom serum antibodies and by a specific antibody to a previously described dermonecrotic toxin. the identified toxin was found to display phospholipase activity and dermonecrotic properties. Additionally, the toxin caused a massive inflammatory response in rabbit skin dermis, evoked platelet aggregation, increased vascular permeability, caused edema and death in mice. These characteristics in combination with functional studies for other dermonecrotic toxins illustrate that a family of dermonecrotic toxins exists, and includes a novel member with high activity that may be useful for future structural and functional studies. (C) 2007 Elsevier B.V. All rights reserved.
Keywords dermonecrotic toxin
phospholipase D
sphingomyelinase
loxosceles
venom
Language English
Date 2008-02-01
Published in Biochimica Et Biophysica Acta-general Subjects. Amsterdam: Elsevier B.V., v. 1780, n. 2, p. 167-178, 2008.
ISSN 0304-4165 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 167-178
Origin http://dx.doi.org/10.1016/j.bbagen.2007.11.007
Access rights Closed access
Type Article
Web of Science ID WOS:000253351600011
URI http://repositorio.unifesp.br/handle/11600/30410

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