Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis

Ruggero De Maria Marchiano, Luisa Lenti, Florence Malisan, Federica D'Agostino, Barbara Tomassini, Ann Zeuner, Maria Rita Rippo, Roberte Testi

Risultato della ricerca: Contributo in rivistaArticolo in rivista

364 Citazioni (Scopus)

Abstract

Gangliosides participate in development and tissue differentiation. Cross-linking of the apoptosis-inducing CD95 protein (also called Fas or APO- 1) in lymphoid and myeloid tumor cells triggered GD3 ganglioside synthesis and transient accumulation. CD95-induced GD3 accumulation depended on integral receptor 'death domains' and on activation of a family of cysteine proteases called caspases. Cell-permeating ceramides, which are potent inducers of apoptosis, also triggered GD3 synthesis. GD3 disrupted mitochondrial transmembrane potential (ΔΨ(m)), and induced apoptosis, in a caspase-independent fashion. Transient overexpression of the GD3 synthase gene directly triggered apoptosis. Pharmacological inhibition of GD3 synthesis and exposure to GD3 synthase antisense oligodeoxynucleotides prevented CD95-induced apoptosis. Thus, GD3 ganglioside mediates the propagation of CD95-generated apoptotic signals in hematopoietic cells.
Lingua originaleEnglish
pagine (da-a)1652-1655
Numero di pagine4
RivistaSCIENCE
Volume277
DOI
Stato di pubblicazionePubblicato - 1997

Keywords

  • Multidisciplinary

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