title: Production of multiple brain-like ganglioside species is dispensable for fas-induced apoptosis of lymphoid cells.
abstract: Activation of an acid sphingomyelinase (aSMase) leading to a biosynthesis of GD3 disialoganglioside has been associated with Fas-induced apoptosis of lymphoid cells. The present study was undertaken to clarify the role of this enzyme in the generation of gangliosides during apoptosis triggered by Fas ligation. The issue was addressed by using aSMase-deficient and aSMase-corrected cell lines derived from Niemann-Pick disease (NPD) patients. Fas cross-linking elicited a rapid production of large amounts of complex a- and b-series species of gangliosides with a pattern and a chromatographic behavior as single bands reminiscent of brain gangliosides. The gangliosides were synthesized within the first ten minutes and completely disappeared within thirty minutes after stimulation. Noteworthy is the observation that GD3 was not the only ganglioside produced. The production of gangliosides and the onset of apoptotic hallmarks occurred similarly in both aSMase-deficient and aSMase-corrected NPD lymphoid cells, indicating that aSMase activation is not accountable for ganglioside generation. Hampering ganglioside production by inhibiting the key enzyme glucosylceramide synthase did not abrogate the apoptotic process. In addition, GM3 synthase-deficient lymphoid cells underwent Fas-induced apoptosis, suggesting that gangliosides are unlikely to play an indispensable role in transducing Fas-induced apoptosis of lymphoid cells.
authors.affiliation: Laboratoire de Recherche Dermatologique, EA4169 Université de Lyon-1, Hôpital Edouard Herriot, Lyon, France.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Popa
authors.forename: Nicole
authors.initials: N
authors.lastname: Therville
authors.forename: Stéphane
authors.initials: S
authors.lastname: Carpentier
authors.forename: Thierry
authors.initials: T
authors.lastname: Levade
authors.forename: Olivier
authors.initials: O
authors.lastname: Cuvillier
authors.forename: Jacques
authors.initials: J
authors.lastname: Portoukalian
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D005434:Flow Cytometry; D005732:Gangliosides / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D013109:Sphingomyelins / Q000378:metabolism; D019014:fas Receptor / Q000494:pharmacology*
chemical_list: D005732:Gangliosides; D013109:Sphingomyelins; D019014:fas Receptor