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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
15
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pubmed:dateCreated |
1997-5-15
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pubmed:abstractText |
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, N-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 N-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-xL conferred resistance to anti-IgM-induced apoptosis, whereas transfection with bcl-2 did not (Gottschalk, A., Boise, L., Thompson, C., and Quintans, J. (1994) Proc. Natl. Acad. Sci. U. S. A. 91, 7350-7354). In this study, these bcl-xL transfectants also displayed increased resistance to exogenous N-acetylsphingosine (C2-ceramide) or N-hexanoylsphingosine (C6-ceramide). However, when challenged with anti-IgM the bcl-xL transfectants produced levels of ceramide similar to wild type cells, suggesting that ceramide formation is upstream of bcl-xL and that it is a major determinant of B-cell death.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Anti-Idiotypic,
http://linkedlifedata.com/resource/pubmed/chemical/Bcl2l1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Carboxylic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramidases,
http://linkedlifedata.com/resource/pubmed/chemical/Ceramides,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Ethanolamines,
http://linkedlifedata.com/resource/pubmed/chemical/Fumonisins,
http://linkedlifedata.com/resource/pubmed/chemical/Mycotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/N-oleoylethanolamine,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelin Phosphodiesterase,
http://linkedlifedata.com/resource/pubmed/chemical/Sphingomyelins,
http://linkedlifedata.com/resource/pubmed/chemical/Teratogens,
http://linkedlifedata.com/resource/pubmed/chemical/anti-IgM,
http://linkedlifedata.com/resource/pubmed/chemical/bcl-X Protein,
http://linkedlifedata.com/resource/pubmed/chemical/fumonisin B1
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pubmed:status |
MEDLINE
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pubmed:month |
Apr
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
11
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pubmed:volume |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
9868-76
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:9092523-Amidohydrolases,
pubmed-meshheading:9092523-Animals,
pubmed-meshheading:9092523-Antibodies, Anti-Idiotypic,
pubmed-meshheading:9092523-Apoptosis,
pubmed-meshheading:9092523-B-Lymphocytes,
pubmed-meshheading:9092523-Carboxylic Acids,
pubmed-meshheading:9092523-Cell Line,
pubmed-meshheading:9092523-Ceramidases,
pubmed-meshheading:9092523-Ceramides,
pubmed-meshheading:9092523-Enzyme Activation,
pubmed-meshheading:9092523-Enzyme Inhibitors,
pubmed-meshheading:9092523-Ethanolamines,
pubmed-meshheading:9092523-Fumonisins,
pubmed-meshheading:9092523-Mice,
pubmed-meshheading:9092523-Mycotoxins,
pubmed-meshheading:9092523-Proto-Oncogene Proteins,
pubmed-meshheading:9092523-Proto-Oncogene Proteins c-bcl-2,
pubmed-meshheading:9092523-Spectrometry, Fluorescence,
pubmed-meshheading:9092523-Sphingomyelin Phosphodiesterase,
pubmed-meshheading:9092523-Sphingomyelins,
pubmed-meshheading:9092523-Teratogens,
pubmed-meshheading:9092523-bcl-X Protein
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pubmed:year |
1997
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pubmed:articleTitle |
Anti-immunoglobulin-induced apoptosis in WEHI 231 cells involves the slow formation of ceramide from sphingomyelin and is blocked by bcl-XL.
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pubmed:affiliation |
Department of Pediatrics, The University of Chicago, Chicago, Illinois 60637, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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