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Suppression of mast cell degranulation by a novel ceramide kinase inhibitor, the F-12509A olefin isomer K1

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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
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.
Type: article (author version)
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

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