|
Hokkaido University Collection of Scholarly and Academic Papers >
Faculty of Pharmaceutical Sciences >
Peer-reviewed Journal Articles, etc >
Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1
| Title: | Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1 |
| Authors: | Kim, Jin-Wook Browse this author | | Inagaki, Yuichi Browse this author | | Mitsutake, Susumu3 Browse this author →KAKEN DB | | Maezawa, Nobuhiro Browse this author | | Katsumura, Shigeo Browse this author | | Ryu, Yeon-Woo Browse this author | | Park, Chang-Seo Browse this author | | Taniguchi, Masaru Browse this author | | Igarashi, Yasuyuki Browse this author →KAKEN DB |
| Authors(alt): | 光武, 進3 |
| Keywords: | Ceramide 1-phosphate | | Ceramide kinase | | Inhibitor | | Degranulation | | Mast cell |
| Issue Date: | 2005 |
| Publisher: | Elsevier B.V. |
| Journal Title: | Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids |
| Volume: | 1738 |
| Issue: | 1-3 |
| Start Page: | 82 |
| End Page: | 90 |
| Publisher DOI: | 10.1016/j.bbalip.2005.10.007 |
| PMID: | 16352467 |
| Abstract: | Antigen-induced degranulation of mast cells plays a pivotal role in allergic and inflammatory responses. Recently, ceramide kinase (CERK) and its phosphorylated product ceramide 1-phosphate (C1P) have emerged as important players in mast cell degranulation. Here, we describe the synthesis of a novel F-12509A olefin isomer, K1, as an effective CERK inhibitor. In vitro kinase assays demonstrated that K1 effectively inhibits CERK without inhibiting sphingosine kinase and diacylglycerol kinase. Treating RBL-2H3 cells with K1 reduced cellular C1P levels to 40% yet had no effect on cell growth. Furthermore, treatment with K1 significantly suppressed both calcium ionophore- and IgE/antigen-induced degranulation, indicating that K1 interferes with signals that happen downstream of Ca2+ mobilization. Finally, we show that K1 affects neither IgE/antigen-induced global tyrosine phosphorylation nor subsequent Ca2+ elevation, suggesting a specificity for CERK-mediated signals. Our novel CERK inhibitor provides a useful tool for studying the biological functions of CERK and C1P. Moreover, to our knowledge, this is the first report demonstrating that inhibition of CERK suppresses IgE/antigen-induced mast cell degranulation. This finding suggests that CERK inhibitors might be a potential therapeutic tool in the treatment of allergic diseases. |
| Relation: | http://www.sciencedirect.com/science/journal/13881981 |
| Type: | article (author version) |
| URI: | http://hdl.handle.net/2115/5800 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
|
Submitter: 光武 進
|
