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Toxicology ; 264(1-2): 80-8, 2009 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-19646502

RESUMO

Parasporin-2 (PS2) is a Bacillus thuringiensis inclusion protein that reacts intensively with human hepatoma cells. This antitumour toxin oligomerizes at the cell surface via binding to lipid rafts, leading to the cell lysis with typical blebs around peripheral cells. We find here that glycosylphosphatidylinositol (GPI)-anchored proteins are involved in the cytocidal actions. Depletion of the cellular cholesterol and loss of sphingolipid in lipid rafts slightly decreased cytolysis by PS2. Beyond those, the cells temporally resisted PS2 with reduction of the toxin binding after GPI-anchored proteins were cleaved off by phosphatidylinositol-specific phospholipase C. PS2 and aerolysin showed individual cytocidal specificity while aerolysin's receptor is GPI-anchored proteins. When we confirmed expression of GPI-anchored proteins on four cell lines, showing different cytotoxicity by PS2, GPI-anchored proteins were evenly expressed on the cells. Therefore, PS2 requires a kind of GPI-anchored proteins for the effective cytolysis.


Assuntos
Antibióticos Antineoplásicos , Endotoxinas/farmacologia , Glicosilfosfatidilinositóis/química , Proteínas/química , Toxinas Bacterianas/química , Toxinas Bacterianas/farmacologia , Western Blotting , Linhagem Celular Tumoral , Membrana Celular/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoplasma/efeitos dos fármacos , Citoplasma/ultraestrutura , Endotoxinas/química , Endotoxinas/metabolismo , Humanos , Microscopia de Fluorescência , Modelos Moleculares , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Citotóxicas Formadoras de Poros/farmacologia
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