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• W1975242912 abstract "Prolonged (>24 h) exposure to anti-IgM (an antigen surrogate that induces membrane cross-linking and apoptosis) induced a 3-fold increase in the mass of endogenous ceramide measured by ³²P labeling by diacylglycerol kinase and a 4-fold increase in ceramide as measured by metabolic labeling with [³H]palmitate in a B-lymphocyte cell line, WEHI 231. This correlated with the induction of apoptosis. Shorter exposure times to anti-IgM (up to 8 h) failed to elicit apoptosis and did not elicit increased ceramide formation. After 8 h, apoptosis occurs concomitantly with ceramide formation over the next 40 h. Further, we showed that exogenous ceramide mimicked anti-IgM-induced apoptosis and that apoptosis was potentiated in serum-free media. Treatment of cells with an inhibitor of ceramide catabolism, <i>N</i>-oleoylethanolamine, increased both ceramide formation and apoptosis and accelerated apoptosis induced by anti-IgM. To examine further how ceramide metabolism is involved in apoptosis, we derived cell lines from a small population of cells resistant to <i>N</i>-oleoylethanolamine. These cell lines were selected based on an altered ceramide metabolic pathway, were resistant to apoptosis induced by anti-IgM, and showed no significant increase in ceramide when challenged with anti-IgM. The basis of this resistance was shown to be the failure to activate neutral sphingomyelinase activity following 24-h treatment with anti-IgM, in contrast to the 2-fold increase in neutral sphingomyelinase activity observed in wild type cells. We have shown previously that transfection of WEHI cells with bcl-x_L conferred resistance to anti-IgM-induced apoptosis, whereas transfection with bcl-2 did not (Gottschalk, A., Boise, L., Thompson, C., and Quintans, J. (1994) <i>Proc. Natl. Acad. Sci. U. S. A</i> 91, 7350-7354). In this study, these bcl-x_L transfectants also displayed increased resistance to exogenous <i>N</i>-acetylsphingosine (C₂-ceramide) or <i>N</i>-hexanoylsphingosine (C₆-ceramide). However, when challenged with anti-IgM the bcl-x_L transfectants produced levels of ceramide similar to wild type cells, suggesting that ceramide formation is upstream of bcl-x_L and that it is a major determinant of B-cell death." @default.
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• W1975242912 date "1997-04-01" @default.
• W1975242912 modified "2023-10-12" @default.
• W1975242912 title "Anti-immunoglobulin-induced Apoptosis in WEHI 231 Cells Involves the Slow Formation of Ceramide from Sphingomyelin and Is Blocked by bcl-xL" @default.
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• W1975242912 doi "https://doi.org/10.1074/jbc.272.15.9868" @default.
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