Role of ceramide in stimulation of the transcription of cytosolic phospholipase A2 and cyclooxygenase 2

Several lines of evidence have implicated lipid second messengers in the signaling pathways evoked by tumor necrosis factor (TNF). In a previous study, we characterized TNF-resistant sublines derived from murine fibrosarcoma L929 cells. and demonstrated that TNF stimulation of arachidonate metabolis...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 1996-03, Vol.220 (3), p.681-686
Main Authors: Hayakawa, M, Jayadev, S, Tsujimoto, M, Hannun, Y A, Ito, F
Format: Article
Language:English
Subjects:
Animals
Base Sequence
Blotting, Northern
Ceramides - biosynthesis
Ceramides - pharmacology
Ceramides - physiology
Cyclooxygenase 2
Cytosol - enzymology
DNA Primers
Gene Expression Regulation, Enzymologic - drug effects
Humans
Isoenzymes - biosynthesis
L Cells (Cell Line)
Membrane Proteins
Mice
Molecular Sequence Data
Phospholipases A - biosynthesis
Phospholipases A2
Polymerase Chain Reaction
Prostaglandin-Endoperoxide Synthases - biosynthesis
Recombinant Proteins - pharmacology
RNA, Messenger - analysis
RNA, Messenger - biosynthesis
Transcription, Genetic - drug effects
Tumor Necrosis Factor-alpha - pharmacology
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Summary:Several lines of evidence have implicated lipid second messengers in the signaling pathways evoked by tumor necrosis factor (TNF). In a previous study, we characterized TNF-resistant sublines derived from murine fibrosarcoma L929 cells. and demonstrated that TNF stimulation of arachidonate metabolism via cytosolic phospholipase A2, (cPLA2) was one of the pathways responsible for the killing of L929 cells. On the other hand, the sphingomyelin cycle, which generates ceramide, is also recognized as a pathway that participates in the apoptosis in certain types of cells. In this study, we evaluated the role of ceramide in TNF-signaling in L929 cells. L929 cells generated ceramide in response to TNF, whereas the TNF-resistant sublines did not. The addition of an exogenous cell-permeable ceramide analogue resulted in the elevated expression of cPLA2 and cyclooxygenase 2 mRNAs in the cells. These results suggest the role of ceramide to amplify the magnitude of signals generated through the PLA2 pathway.
ISSN:0006-291X
DOI:10.1006/bbrc.1996.0464