Involvement of phospholipid-related enzymes and transporters in lung diseases

• Project/Area Number: 24790805
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Respiratory organ internal medicine
• Research Institution: 独立行政法人国立国際医療研究センター
• Principal Investigator: HARAYAMA TAKESHI 独立行政法人国立国際医療研究センター, 脂質シグナリングプロジェクト, 研究員 (50610218)
• Project Period (FY): 2012-04-01 – 2014-03-31
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
• Keywords: リン脂質 / ホスファチジルコリン / 酵素 / 肺サーファクタント / アシル基転移酵素 / 急性肺障害 / 脂質代謝 / リピドミクス / 酵素学 / 炎症

Research Abstract

To investigate the functions of phospholipids in the lung, we generated mice that lack a phospholipid-metabolizing enzyme, LPCAT1. We investigated the role of LPCAT1 during pulmonary diseases, and found that LPCAT1-deficient mice have altered pulmonary surfactant (a surface active material that prevents alveolar collapse in the lung) function. This property rendered LPCAT1-deficient mice highly susceptible to acute lung injury.
In addition, we found how multiple phospholipid-metabolizing enzymes regulate phospholipid composition in various tissues. These findings will lead to an understanding of the relationship between various diseases and phospholipid metabolism.

Research Products

• [Journal Article] Landsサイクルとサーファクタント代謝 (2014)
  • Author(s): 原山武士、清水孝雄
  • Journal Title: 生体の科学(公益財団法人金原一郎医学医療振興財団) Volume: 65巻4号(掲載予定)
• [Journal Article] TDAG8 activation inhibits osteoclastic bone resorption (2014)
  • Author(s): Hikiji, H., Endo, D., Horie, K., Harayama, T., Akahoshi, N., Igarashi, H., Kihara, Y., Yanagida, K., Takeda, J., Koji, T., Shimizu, T., and Ishii, S
  • Journal Title: FASEB J Volume: 28 Issue: 2 Pages: 871-879
  • DOI: 10.1096/fj.13-233106
  • Peer Reviewed
• [Journal Article] Lysophospholipid acyltransferases mediate phosphatidylcholine diversification to achieve the physical properties required in vivo (2014)
  • Author(s): Takeshi Harayama, Miki Eto, Hideo Shindou, Yoshihiro Kita, Eiji Otsubo, Daisuke Hishikawa, Satoshi Ishii, Kenji Sakimura, Masayoshi Mishina, and Takao Shimizu
  • Journal Title: Cell Metabolism Volume: 印刷中
  • Peer Reviewed
• [Journal Article] Generation of membrane diversity bylysophospholipid acyltransferases (2013)
  • Author(s): Hideo Shindou, Daisuke Hishikawa, TakeshiHarayama, Miki Eto, and Takao Shimizu
  • Journal Title: The Journal of Biochemistry(OxfordJournals) Volume: Vol.154 Issue: 1 Pages: 21-28
  • DOI: 10.1093/jb/mvt048
• [Journal Article] Identification of Sec14-like 3 as a novel lipid-packing sensor in the lung (2013)
  • Author(s): Daisuke Hishikawa, Hideo Shindou, Takeshi Harayama, Rie Ogasawara, Akira Suwabe, and Takao Shimizu
  • Journal Title: The FASEB journal Volume: 27 Issue: 12 Pages: 5131-5140
  • DOI: 10.1096/fj.13-237941
  • Peer Reviewed
• [Journal Article] 血小板活性化因子(PAF)生合成酵素(LPCATs)阻害剤の検討 (2013)
  • Author(s): 垂井愛、進藤英雄、森本亮、衛藤樹、原山武士、長瀬隆英、清水孝雄
  • Journal Title: 分子呼吸器病 Volume: 71 Pages: 146-148
• [Journal Article] Palmitoleate is a mitogen, formed upon stimulation with growth factors, and converted to palmitoleoyl-phosphatidylinositol. (2012)
  • Author(s): Koeberle A, Shindou H, Harayama T, Shimizu T
  • Journal Title: J. Biol. Chem. Volume: 287 Issue: 32 Pages: 27244-54
  • DOI: 10.1074/jbc.m111.274829
  • Peer Reviewed
• [Journal Article] Lysophosphatidylcholine acyltransferase 3 is the key enzyme for incorporating arachidonic acid into glycerophospholipids during adipocyte differentiation. (2012)
  • Author(s): Eto M, Shindou H, Koeberle A, Harayama T, Yanagida K, Shimizu T
  • Journal Title: Int J Mol Sci. Volume: 13 Issue: 12 Pages: 16267-80
  • DOI: 10.3390/ijms131216267
  • Peer Reviewed
• [Journal Article] Lysophospholipid Acyltransferases Mediate Phosphatidylcholine Diversification to Achieve the Physical Properties Required InVivo
  • Author(s): Takeshi Harayama, Miki Eto, Hideo Shindou, Yoshihiro Kita, Eiji Otsubo, Daisuke Hishikawa, Satoshi Ishii, Kenji Sakimura, Masayoshi Mishina, and TakaoShimizu
  • Journal Title: Cell Metabolism(Cell Press) Volume: (掲載決定)
  • Peer Reviewed
• [Presentation] Discovery of a selective inhibitor for the PAF biosynthetic enzyme lysophosphatidylcholine acyltransferase 2 (2013)
  • Author(s): Megumi Tarui, Hideo Shindou, Ryo Morimoto, Miki Eto, Takeshi Harayama, Kazuo Kumagai, Testuo Nagano, Takahide Nagase, and Takao Shimizu
  • Organizer: 13th International Conference on Bioactive Lipids in Cancer, Inflammation and Related Diseases
  • Place of Presentation: San Juan, Puerto Rico
• [Presentation] Glycerophospholipid biosynthesis by lysophospholipidacyltransferases in the Lands' cycle (2012)
  • Author(s): Hideo Shindou, Daisuke Hishikawa, Takeshi Harayama, Miki, Eto, Ryo Morimoto, and TakaoShimizu
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場、マリンメッセ福岡、福岡
  • Year and Date: 2012-12-15
• [Presentation] 血小板活性化因子（PAF）生合成酵素（LPCATs）阻害剤の検討 (2012)
  • Author(s): 垂井愛、進藤英雄、森本亮、衛藤樹、原山武士、長瀬隆英、清水孝雄
  • Organizer: 第11回肺サーファクタント分子病態研究会
  • Place of Presentation: 札幌医科大学記念ホール
• [Presentation] Glycerophospholipid biosynthesis by lysophospholipid acyltransferases in the Lands’ cycle (2012)
  • Author(s): Hideo Shindou, Daisuke Hishikawa, Takeshi Harayama, Miki, Eto, Ryo Morimoto, and Takao Shimizu
  • Organizer: 第85回日本生化学会大会
  • Place of Presentation: 福岡国際会議場
• [Remarks] 国立国際医療研究センター研究所のホームページ
  • URL: http://www.rincgm.jp/
• [Remarks] 国立国際医療研究センター研究所脂質シグナリングプロジェクトのホームページ
  • URL: http://www.ncgmlipidsp.jp/
• [Remarks] 国立国際医療研究センター脂質シグナリングプロジェクトwebページ
  • URL: http://www.ncgmlipidsp.jp/