Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
J Oral Sci ; 47(1): 43-51, 2005 Mar.
Article in English | MEDLINE | ID: mdl-15881228

ABSTRACT

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.


Subject(s)
Ceramides/pharmacology , Lysophospholipids/physiology , Osteoblasts/metabolism , Second Messenger Systems/physiology , Sphingosine/analogs & derivatives , Sphingosine/physiology , Transcription Factor AP-1/biosynthesis , Tumor Necrosis Factor-alpha/pharmacology , 3T3 Cells , Animals , Blotting, Northern , Ceramides/physiology , Chemokine CCL2/genetics , Electrophoresis, Polyacrylamide Gel , Enzyme Inhibitors/pharmacology , Gene Expression/drug effects , Genes, fos , Genes, jun , Mice , Mice, Inbred C57BL , Morpholines/pharmacology , Propanolamines/pharmacology , Pyrrolidines/pharmacology , Recombinant Proteins/pharmacology , Sphingomyelin Phosphodiesterase/metabolism , Sphingomyelin Phosphodiesterase/pharmacology , Tetradecanoylphorbol Acetate/metabolism , Tumor Necrosis Factor-alpha/physiology
SELECTION OF CITATIONS
SEARCH DETAIL
...