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 cell
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概要
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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. <I>DL-threo</I>-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 (<I>N</I>-acetylsphingosine, <I>N</I>-hexanoylsphingosine or <I>N</I>-octanoylsphingosine) stimulated expression of the c-fos and c-jun genes and nuclear protein binding to TRE. Interestingly, <I>DL-threo</I>-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)
著者
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Takeshita Akira
Department Of Cardiology Faculty Of Medicine Kyushu University
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Takano Akiko
Department Of Internal Medicine Ii Hokkaido University Graduate School Of Medicine
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Tanaka Susumu
Department Of Cardiology The Second Tokyo National Hospital
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Shinoda Hiroyuki
Department Of Dermatology Hokkaido University Graduate School Of Medicine
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Suetsugu Mayumi
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Nakabayashi Yasuo
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Matsumoto Ken
Research Laboratory, Nissui Pharmaceutical Company, Ltd. Research Laboratory
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Miyazawa Kei
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Tanaka Sonoji
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Endo Hiromasa
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Ueyama Yoshifumi
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Hanzawa Akiko
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Suda Yoko
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Kanegae Haruhide
Department of Orthodontics, Meikai University School of Dentistry
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Yasui Toshikazu
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Nakabayashi Yasuo
Department of Chemistry, Faculty of Science, Tohoku University
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Shinoda Hiroyuki
Department of Applied Chemistry, Faculty of Science and Engineering, Waseda University
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Takeshita Akira
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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Tanaka Susumu
Department of Applied Physics, Tohoku University, Sendai 980-8579, Japan
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Tanaka Susumu
Department of Oral Health and Preventive Dentistry, Meikai University School of Dentistry
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