Regulation of inflammation by sphingolipid salvage pathway

• Project/Area Number: 23790366
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pathological medical chemistry
• Research Institution: Tohoku University (2012); Tottori University (2011)
• Principal Investigator: KITATANI Kazuyuki 東北大学, 東北メディカル・メガバンク機構, 助教 (40539235)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2011: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: セラミド / p38 / p38δ / 炎症 / スフィンゴ脂質 / 細胞運動 / 細胞遊走 / GBA1 / ゴーシェ病

Research Abstract

The PI hypothesized that p38δ and sphingolipid salvage pathway regulate inflammation. The PI identified p38δ-controlled genes responsible for inflammation. The PI discovered that short-chain C_6-ceramide decreased cell motility. Most of exogenous C6-ceramide can be converted to sphingosine which in turn is reacylated to form long chain ceramide. Inhibition of ceramide salvage by fumonisin B1 restored decreased cell motility with C6-ceramide. Those results raise the possibility that ceramide synthesis through the salvage pathway is responsible for inhibiting cell motility. This study provides new insight for developing novel therapeutic approaches to inflammation -involving disorders.

Research Products

• [Journal Article] Regulation of cell migration by sphingomyelin synthases : sphingomyelin in lipid rafts decreases responsiveness to signaling by the CXCL12/CXCR4 pathway (2012)
  • Author(s): Asano S, Kitatani K, Taniguchi M, Hashimoto M, Zama K, Mitsutake S, Igarashi Y, Takeya H, Kigawa J, Hayashi A, Umehara H and Okazaki T
  • Journal Title: Molecular and cellular biology Volume: 32 Issue: 16 Pages: 3242-3252
  • DOI: 10.1128/mcb.00121-12
  • Peer Reviewed
• [Journal Article] Identification and characterization of PP2C activation by ceramide (2012)
  • Author(s): Perry. D.M., Kitatani K., Roddy P., El-Osta M., Hannun Y.A.
  • Journal Title: J. Lipid Res Volume: 53 Issue: 8 Pages: 1513-1521
  • DOI: 10.1194/jlr.m025395
  • Peer Reviewed
• [Journal Article] Regulation of autophagy and its associated cell death by sphingolipid rheostat: Reciprocal role in ceramide and sphingosine-1-phosphate in the mTOR pathway (2012)
  • Author(s): Taniguchi M., Kitatani K., Kondo T., Hashimoto-Nishimura M., Asano S., Hayashi A., Mitsutake S., Igarashi Y., Umehara H., Takeya H., Kigawa J. and Okazaki T.
  • Journal Title: J. Biol. Chem Volume: 287 Issue: 47 Pages: 39898-39910
  • DOI: 10.1074/jbc.m112.416552
  • Peer Reviewed
• [Journal Article] Regulation of autophagy and its associated cell death by sphingolipid rheostat: Reciprocal role in ceramide and sphingosine-1-phosphate in the mTOR pathway (2012)
  • Author(s): Taniguchi M et al
  • Journal Title: J. Biol. Chem. Volume: 287 Pages: 39898-39910
  • Peer Reviewed
• [Journal Article] Identification and characterization of PP2C activation by ceramide (2012)
  • Author(s): Perry. D.M. et al.
  • Journal Title: J. Lipid Res. Volume: 53 Pages: 1513-1521
  • Peer Reviewed
• [Journal Article] Regulation of cell migration by sphingomyelin synthases: sphingomyelin in lipid rafts decrease responsiveness to signaling by the CXCL12/CXCR4 pathway (2012)
  • Author(s): Asano S. et al
  • Journal Title: Mol. Cell. Biol. Volume: 32 Pages: 3242-3252
  • Peer Reviewed
• [Journal Article] Regulation of death and growth signals at the plasma membrane by sphongomyelin synthesis: implications for hematological malignancies (2011)
  • Author(s): Lafont E., Kitatani K., Okazaki T., and Segui B.
  • Journal Title: Recent Pat. Anticancer Drug Discov Volume: 6 Issue: 3 Pages: 324-333
  • DOI: 10.2174/157489211796957801
• [Journal Article] セラミドを中心としたスフィンゴ脂質代謝 (2011)
  • Author(s): 北谷和之,浅野智志,橋本真由美,谷口真,岡崎俊郎
  • Journal Title: 生化学 Volume: 83 Pages: 495-505
  • NAID: 10029068896
• [Journal Article] SMS1-generated sphingomyelin plays an important role in transferring trafficking and cell proliferation (2011)
  • Author(s): Kitatani K., Abdel Shakor A.B., Taniguchi M., Hashimoto M., Asano S., Hayashi A., Nomura K., Bielawski J., Bielawska A., Watanabe K., Kobayashi T., Igarashi Y., Umehara H.
  • Journal Title: J. Biol. Chem. Volume: 286 Pages: 36053-36062
  • Peer Reviewed
• [Presentation] p38δ is a novel target for anti-inflammation therapy of Gaucher 's disease (2012)
  • Author(s): Kitatani K.
  • Organizer: 4th Gaucher Leadership Forum
  • Place of Presentation: Munich, Germany
  • Year and Date: 2012-09-22
• [Presentation] p38δ is a novel target for anti-inflammation therapy of Gaucher’s disease (2012)
  • Author(s): Kitatani K.
  • Organizer: 4th Gaucher Leadership Forum, (2012.9)
  • Place of Presentation: Munich, Germany
  • Invited
• [Presentation] p38 activation in Gaucher's disease model mice (2011)
  • Author(s): Kitatani K., Perry D., Wada M., Sheldon K., Sun Y., Bielawski J., Anneli V., Obeid LM.,Okazaki T., Grabowski G., Hannun YH.
  • Organizer: 第6回スフィンゴテラピー研究会
  • Place of Presentation: 米子
  • Year and Date: 2011-07-16
• [Presentation] スフィゴミエリンによる走化性運動の制御 (2011)
  • Author(s): 浅野智志,北谷和之,谷口真,橋本真由美,武谷浩之,座間宏太,光武進,五十嵐靖之,清川悦子,松田道行,岡崎俊郎
  • Organizer: 第53回脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-13
• [Presentation] Ceramide-mediated XIAP degradation through cathepsin B in IL-2-deprived natural killer cells (2011)
  • Author(s): 谷口真, 北谷和之,林輝,田口良光,橋 本真由美,浅野智志,梅原久範,武谷浩之, 岡崎俊郎
  • Organizer: 第53回脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2011-05-12
• [Book] "セラミドの細胞内機能概論スフィンゴミエリン合成酵素ファミリー"セラミド-基礎と応用- (2011)
  • Author(s): 北谷和之,岡崎俊郎
  • Publisher: 食品化学新聞社
• [Patent(Industrial Property Rights)] スフィンコ脂質の製造方法 (2012)
  • Inventor(s): 北谷和之、岡崎俊朗、平田みよ、北垣浩志
  • Industrial Property Rights Holder: 北谷和之、岡崎俊朗、平田みよ、北垣浩志
  • Industrial Property Number: 2012-090774
  • Filing Date: 2012-05-16
• [Patent(Industrial Property Rights)] スフィンゴ脂質の製造方法 (2012)
  • Inventor(s): 北谷和之、岡崎俊朗、平田みよ、北垣浩志
  • Industrial Property Rights Holder: 北谷和之、岡崎俊朗、平田みよ、北垣浩志
  • Industrial Property Rights Type: 特許
  • Filing Date: 2012-05-16