Document Detail

Sphingosine 1-phosphate acts as a signal molecule in ceramide signal transduction of TNF-alpha-induced activator protein-1 in osteoblastic cell line MC3T3-E1 cells.
MedLine Citation:
PMID:  15881228     Owner:  NLM     Status:  MEDLINE    
We previously demonstrated that tumor necrosis factor (TNF)-alpha stimulated the production of activation protein (AP)-1, a transcriptional factor, in mouse osteoblastic MC3T3-E1 cells. Recent studies have shown the importance of ceramide and its metabolites as signal molecules for TNF-alpha-induced gene expression in several cell types. Therefore, our interest was to investigate whether sphingosine metabolites are involved in TNF-alpha-induced signaling in MC3T3-E1 cells. DL-threo-1-phenyl-2-hexadecanoyl-amino-3-pyrrolidino-1-propanol (PPPP), which causes accumulation of intracellular ceramide, stimulated the TNF-alpha-induced expression of the c-fos and c-jun genes. Gel shift assay clearly showed that PPPP increased the cytokine-induced specific binding of nuclear proteins to the 12-tetra-decanoyl phorbol 13-acetate-responsive element (TRE), a consensus sequence for AP-1. In addition, cell-permeable ceramide (N-acetylsphingosine, N-hexanoylsphingosine or N-octanoylsphingosine) stimulated expression of the c-fos and c-jun genes and nuclear protein binding to TRE. Interestingly, DL-threo-dihydrosphingosine (DHS), an inhibitor of sphingosine kinase, clearly blocked the ceramide analogue-induced stimulation. Sphingosine 1-phosphate (SPP) actually induced expression of these oncogenes and activated AP-1. Although TNF-alpha stimulated the AP-1-mediated expression of the monocyte chemoattractant JE/MCP-1, this stimulation was inhibited by DHS. SPP also stimulated JE/MCP-1 gene expression. The present study thus suggests that SPP acts as a signal molecule in ceramide-dependent signal transduction in TNF-alpha-induced AP-1 in osteoblastic MC3T3-E1 cells.
Akira Takeshita; Hiroyuki Shinoda; Yasuo Nakabayashi; Akiko Takano; Ken Matsumoto; Mayumi Suetsugu; Kei Miyazawa; Sonoji Tanaka; Hiromasa Endo; Susumu Tanaka; Yoshifumi Ueyama; Akiko Hanzawa; Yoko Suda; Haruhide Kanegae; Toshikazu Yasui
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Journal of oral science     Volume:  47     ISSN:  1343-4934     ISO Abbreviation:  J Oral Sci     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-05-09     Completed Date:  2005-05-24     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9808942     Medline TA:  J Oral Sci     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  43-51     Citation Subset:  D; IM    
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry, Keyakidai, Sakado-city, Saitama 350-0283, Japan.
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MeSH Terms
3T3 Cells
Blotting, Northern
Ceramides / pharmacology*,  physiology
Chemokine CCL2 / genetics
Electrophoresis, Polyacrylamide Gel
Enzyme Inhibitors / pharmacology
Gene Expression / drug effects
Genes, fos
Genes, jun
Lysophospholipids / physiology*
Mice, Inbred C57BL
Morpholines / pharmacology
Osteoblasts / metabolism*
Propanolamines / pharmacology
Pyrrolidines / pharmacology
Recombinant Proteins / pharmacology
Second Messenger Systems / physiology*
Sphingomyelin Phosphodiesterase / metabolism,  pharmacology
Sphingosine / analogs & derivatives*,  physiology*
Tetradecanoylphorbol Acetate / metabolism
Transcription Factor AP-1 / biosynthesis*
Tumor Necrosis Factor-alpha / pharmacology*,  physiology
Reg. No./Substance:
0/1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol; 0/Ceramides; 0/Chemokine CCL2; 0/Enzyme Inhibitors; 0/Lysophospholipids; 0/Morpholines; 0/Propanolamines; 0/Pyrrolidines; 0/Recombinant Proteins; 0/Transcription Factor AP-1; 0/Tumor Necrosis Factor-alpha; 123-78-4/Sphingosine; 16561-29-8/Tetradecanoylphorbol Acetate; 26993-30-6/sphingosine 1-phosphate; 73257-80-4/RV 538; EC Phosphodiesterase

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