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

Abstract:

:In 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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Colell A,Morales A,Fernández-Checa JC,García-Ruiz C

doi

10.1016/s0014-5793(02)03140-x

keywords:

subject

Has Abstract

pub_date

2002-08-28 00:00:00

pages

135-41

issue

1-3

eissn

0014-5793

issn

1873-3468

pii

S001457930203140X

journal_volume

526

pub_type

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