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
| Autor: | Akira Takeshita, Akiko Takano, Akiko Hanzawa, Susumu Tanaka, Mayumi Suetsugu, Kei Miyazawa, Hiroyuki Shinoda, Yoshifumi Ueyama, Toshikazu Yasui, Hiromasa Endo, Yoko Suda, Ken Matsumoto, Yasuo Nakabayashi, Sonoji Tanaka, Haruhide Kanegae |
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| Rok vydání: | 2005 |
| Předmět: |
Ceramide
Pyrrolidines Morpholines Sphingosine kinase Gene Expression Biology Ceramides Second Messenger Systems Propanolamines chemistry.chemical_compound Mice Genes jun Sphingosine Gene expression Animals Sphingosine-1-phosphate Enzyme Inhibitors General Dentistry Chemokine CCL2 Osteoblasts Tumor Necrosis Factor-alpha Genes fos Lipid signaling 3T3 Cells Blotting Northern Recombinant Proteins Cell biology Mice Inbred C57BL Transcription Factor AP-1 Sphingomyelin Phosphodiesterase chemistry Tetradecanoylphorbol Acetate Electrophoresis Polyacrylamide Gel Signal transduction Lysophospholipids Sphingomyelin |
| Zdroj: | Journal of oral science. 47(1) |
| ISSN: | 1343-4934 |
| Popis: | We previously demonstrated that tumor necrosis factor (TNF)-α 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-α-induced gene expression in several cell types. Therefore, our interest was to investigate whether sphingosine metabolites are involved in TNF-α-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-α-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-α 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-α-induced AP-1 in osteoblastic MC3T3-E1 cells. (J. Oral Sci. 47, 43-51, 2005) |
| Databáze: | OpenAIRE |
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