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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1652-1655
Number of pages4
JournalScience
Volume277
Issue number5332
DOIs
Publication statusPublished - Sep 12 1997

ASJC Scopus subject areas

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    De Maria, R., Lenti, L., Malisan, F., D'Agostino, F., Tomassini, B., Zeuner, A., Rippo, M. R., & Testi, R. (1997). Requirement for GD3 ganglioside in CD95- and ceramide-induced apoptosis. Science, 277(5332), 1652-1655. https://doi.org/10.1126/science.277.5332.1652