A cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase C

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dc.creatorFlores Díaz, Marietta
dc.creatorAlape Girón, Alberto
dc.creatorClark, Graeme
dc.creatorCatimel, Bruno
dc.creatorHirabayashi, Yoshio
dc.creatorNice, Ed
dc.creatorGutiérrez, José María
dc.creatorTitball, Richard
dc.creatorThelestam, Mónica
dc.date.accessioned2017-01-09T20:07:57Z
dc.date.available2017-01-09T20:07:57Z
dc.date.issued2005-07-22
dc.description.abstractClostridium perfringens phospholipase C (Cp-PLC), also called alpha-toxin, is the major virulence factor in the pathogenesis of gas gangrene. Previously, a cellular UDP-Glc deficiency was related with a hypersensitivity to the cytotoxic effect of Cp-PLC. Because UDP-Glc is required in the synthesis of proteoglycans, N-linked glycoproteins, and glycosphingolipids, the role of these gly-coconjugates in the cellular sensitivity to Cp-PLC was studied. The cellular sensitivity to Cp-PLC was significantly enhanced by glycosphingolipid synthesis inhibitors, and a mutant cell line deficient in gangliosides was found to be hypersensitive to Cp-PLC. Gangliosides protected hypersensitive cells from the cytotoxic effect of Cp-PLC and prevented its membrane-disrupting effect on artificial membranes. Removal of sialic acids by C. perfringens sialidase increases the sensitivity of cultured cells to Cp-PLC and intramuscular co-injection of C. perfringens sialidase, and Cp-PLC in mice potentiates the myotoxic effect of the latter. This work demonstrated that a reduction in gangliosides renders cells more susceptible to the membrane damage caused by Cp-PLC and revealed a previously unrecognized synergism between Cp-PLC and C. perfringens sialidase, providing new insights toward understanding the pathogenesis of clostridial myonecrosis.es_ES
dc.description.procedenceUCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias de la Salud::Instituto Clodomiro Picado (ICP)es_ES
dc.identifier.citationhttp://www.jbc.org/content/280/29/26680.long
dc.identifier.doi10.1074/jbc.M500278200es_ES
dc.identifier.issn1083-351X
dc.identifier.urihttps://hdl.handle.net/10669/29415
dc.language.isoen_USes_ES
dc.rightsacceso abierto
dc.sourceThe Journal of Biological Chemistry; Volumen 280, Número 29. 2005es_ES
dc.subjectAnimalses_ES
dc.subjectCell Linees_ES
dc.subjectCell Membranees_ES
dc.subjectClostridium Perfringenses_ES
dc.subjectDrug Synergismes_ES
dc.subjectGangliosideses_ES
dc.subjectHumanses_ES
dc.subjectHypersensitivityes_ES
dc.subjectLiposomeses_ES
dc.subjectMicees_ES
dc.subjectNeuraminidasees_ES
dc.subjectSialic Acidses_ES
dc.subjectType C Phospholipaseses_ES
dc.titleA cellular deficiency of gangliosides causes hypersensitivity to Clostridium perfringens phospholipase Ces_ES
dc.typeartículo original

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