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Lysosomal sphingomyelinase is not solicited for apoptosis signaling
Author(s) -
Bezombes Christine,
Ségui Bruno,
Cuvillier Olivier,
Bruno Alain P.,
UroCoste Emmanuelle,
Gouazé Valérie,
AndrieuAbadie Nathalie,
Carpentier Stéphane,
Laurent Guy,
Salvayre Robert,
Jaffrézou JeanPierre,
Levade Thierry
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0466fje
Subject(s) - acid sphingomyelinase , ceramide , apoptosis , sphingomyelin , lipid signaling , sphingomyelin phosphodiesterase , microbiology and biotechnology , programmed cell death , chemistry , cell culture , sphingolipid , enzyme , cancer research , biology , biochemistry , cholesterol , genetics
Stress‐induced activation of an acidic sphingomyelinase leading to generation of ceramide, an important lipid mediator, has been associated with apoptosis; however, the implication of this hydrolase has been questioned. The present study aimed at re‐evaluating the role of this lysosomal enzyme in apoptosis initiated by different apoptotic inducers. The sensitivity of a series of acid sphingomyelinase‐deficient cell lines derived from Niemann‐Pick disease patients to stress‐induced apoptosis was investigated. We have now shown that stress stimuli, such as anthracyclines, ionizing radiation, and Fas ligation trigger similar apoptotic hallmarks in normal and acid sphingomyelinase‐deficient cell lines. Retrovirus‐mediated gene correction of enzyme deficiency in Niemann‐Pick cells does not modify response to apoptosis. Ceramide production is comparable in normal and Niemann‐Pick cells, and increased activity of neutral sphingomyelinase is observed. Thus, our findings cast serious doubts that lysosomal sphingomyelinase activation is responsible for stress‐induced apoptosis of cultured cells.