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Title

Ceramide generated by acidic sphingomyelinase contributes to tumor necrosis factor-α-mediated apoptosis in human colon HT-29 cells through glycosphingolipids formation: Possible role of ganglioside GD3

AuthorsColell Riera, Anna ; Morales, Albert ; Fernández-Checa, José C. ; García-Ruiz, Carmen
KeywordsGlycosphingolipid
Mitochondrion
Death ligand
Ceramide
Apoptosis
Issue Date28-Aug-2002
PublisherElsevier
CitationFEBS Letters 526(1-3): 135-141 (2002)
AbstractIn the present study we assessed the contribution of acidic sphingomyelinase (ASMase), a ceramide generating enzyme, in tumor necrosis factor (TNF)-mediated apoptosis in human colon HT-29 cells. TNF induced apoptosis in HT-29 cells in a time- and dose-dependent fashion. Downregulation of the active endogenous ASMase form prevented TNF-stimulated ASMase activity and apoptosis. Furthermore, inhibition of glucosylceramide synthase, which blunted TNF-stimulated GD3 levels, abolished TNF-mediated cell death. Immunocytochemical staining revealed the co-localization of GD3 with mitochondria induced by TNF. The knockdown of targeted GD3 synthase by antisense expression vector protected HT-29 cells against TNF-induced cell death. Thus, ASMase plays a key role in TNF-induced cell death in human colon epithelial cells possibly through GD3 generation. © 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Publisher version (URL)http://dx.doi.org/10.1016/S0014-5793(02)03140-X
URIhttp://hdl.handle.net/10261/111522
DOI10.1016/S0014-5793(02)03140-X
Identifiersdoi: 10.1016/S0014-5793(02)03140-X
issn: 0014-5793
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