The bactericidal effect of human secreted group IID phospholipase A(2) results from both hydrolytic and non-hydrolytic activities

Autor(es)

Fonseca-Maldonado, Raquel ^[1] ; Ferreira, Tatiana Lopes ^[1] ; Ward, Richard J. ^[2]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, FMRP USP, Dept Biochem & Immunol, BR-14040901 Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, FFCLRP USP, Dept Chem, BR-14040901 Ribeirao Preto, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Biochimie; v. 94, n. 6, p. 1437-1440, JUN 2012.
• Citações Web of Science: 3

Resumo

The Human Secreted Group IID Phospholipase A(2) (hsPLA2GIID) may be involved in the human acute immune response. Here we have demonstrated that the hsPLA2GIID presents bactericidal and Ca2+-independent liposome membrane-damaging activities and we have compared these effects with the catalytic activity of active-site mutants of the protein. All mutants showed reduced hydrolytic activity against DOPC:DOPG liposome membranes, however bactericidal effects against Escherichia coli and Micrococcus luteus were less affected, with the D49K mutant retaining 30% killing of the Gram-negative bacteria at a concentration of 10 mu g/mL despite the absence of catalytic activity. The H48Q mutant maintained Ca2+-independent membrane-damaging activity whereas the G30S and D49K mutants were approximately 50% of the wild-type protein, demonstrating that phospholipid bilayer permeabilization by the hsPLA2GIID is independent of catalytic activity. We suggest that this Ca2+-independent damaging activity may play a role in the bactericidal function of the protein. (C) 2012 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 02/12746-2 - Investigação de mudanças conformacionais de bothropstoxina I (PLA2-Lys49) do veneno de Bothrops jararacussu em associação com membranas artificiais
• Beneficiário: Tatiana Lopes Ferreira
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto
• Processo FAPESP: 06/54285-2 - Atividade da fosfolipase A2 secretada humana do grupo IID (hsPLA2-IID) contra membranas artificiais e biológicas
• Beneficiário: Raquel Fonseca Maldonado
• Modalidade de apoio: Bolsas no Brasil - Mestrado