Lipocalin-type Prostaglandin D synthase; transporter and scavenger for Prostaglandin D2

• Project/Area Number: 19590094
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Osaka Bioscience Institute
• Principal Investigator: ARITAKE Kosuke Osaka Bioscience Institute, 分子行動生物学部門, 研究員 (70390804)
• Co-Investigator(Kenkyū-buntansha): FUJIMORI Ko 大阪薬科大学, 薬学部生体防御研究室, 講師 (70425453) ; HUANG Zhi-li , 分子行動生物学部門, 研究員 (10321704) ; HOSHIKAWA Yumiko , 分子行動生物学部門, 研究員 (10390808) ; MARUYAMA Toshihiko , 分子行動生物学部門, 研究員 (70414133)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2007: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
• Keywords: プロスタグランジンD_2 / リポカリン / プロスタグランジンD合成酵素

Research Abstract

酵素活性と低分子化合物輸送能を有する多機能タンパク質のリポカリン型プロスタグランジン(PG)D2合成酵素(L-PGDS)と、酵素反応生成物PGD2の相互作用を調べたところ、LPGDSはPGD2と可逆的に結合する一方で、PGD2の分解物の15d-PGJ2 とは不可逆的に共有結合することが判明した。L-PGDSは細胞内ではPGD2産生を触媒し、細胞外ではPGD2を安定的に標的組織まで輸送し、分解物を結合して不活化する作用を有すると考えられた。

Research Products

• [Journal Article] Biochemical, functional, and pharmacological characterization of AT-56, an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase (2009)
  • Author(s): Irikura D, Aritake K, Nagata N, Maruyama T, Shimamoto S, Urade Y
  • Journal Title: J Biol Chem 284(12) Pages: 7623-30
• [Journal Article] Biochemical, functional, and pharmacological characterization of AT-56, an orally active and selective inhibitor of lipocalin-type prostaglandin D synthase (2009)
  • Author(s): Aritake K
  • Journal Title: J Biol Chem. 284(12) Pages: 7623-30
  • Peer Reviewed
• [Journal Article] Role of prostaglandin D2 receptor DP as a suppressor of tumor hyperpermeability and angiogenesis in vivo (2008)
  • Author(s): Murata T, Lin MI, Aritake K, Matsumoto S, Narumiya S, Ozaki H, Urade Y, Hori M, Sessa WC
  • Journal Title: Proc Natl Acad Sci U S A 105(50) Pages: 20009-14
• [Journal Article] Enhancement of prostaglandin D2 production through cyclooxygenase-2 and lipocalin-type prostaglandin D synthase by upstream stimulatory factor 1 in human brain-derived TE671 cells under serum starvation (2008)
  • Author(s): Fujimori K, Aritake K, Urade Y
  • Journal Title: Gene 426(1-2) Pages: 72-80
• [Journal Article] Lipopolysaccharide induces macrophage migration via prostaglandin D2 and prostaglandin E2 (2008)
  • Author(s): Tajima T, Murata T, Aritake K, Urade Y, Hirai H, Nakamura M, Ozaki H, Hori M
  • Journal Title: J Pharmacol Exp Ther 326(2) Pages: 493-501
• [Journal Article] Role of prostaglandin D_2 receptor DP as a suppressor of tumor hynerpermeability and angiogenesis in vivo (2008)
  • Author(s): Murata T
  • Journal Title: Proc Natl Acad Sci USA 105(50) Pages: 20009-14
  • Peer Reviewed
• [Journal Article] Enhancement of prostaglandin D_2, production through cyclooxyenase-2 and lipocalin-type prostaglandin D synthase by upstream stimulatory factor 1 in human brain-derived TE671 cells under serum starvation (2008)
  • Author(s): Fujimori K
  • Journal Title: Gene 426(1-2) Pages: 72-80
  • Peer Reviewed
• [Journal Article] Lipopolysaccharide induces macrophage migration via prostaglandin D_2 and prostaglandin E_2 (2008)
  • Author(s): Tajima T
  • Journal Title: J Pharmacol Exp Ther. 326(2) Pages: 493-501
  • Peer Reviewed
• [Journal Article] NMR solution structure of lipocalin-type prostaglandin D synthase : evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the central cavity (2007)
  • Author(s): Shimamoto S, Yoshida T, Inui T, Gohda K, Kobayashi Y, Fujimori K, Tsurumura T, Aritake K, Urade Y, Ohkubo T
  • Journal Title: J Biol Chem 282(43) Pages: 31373-9
• [Journal Article] A novel pathway to enhance adipocyte differentiation of 3T3-L1 cells by up-regulation of lipocalin-type prostaglandin D synthase mediated by liver X receptor-activated sterol regulatory element-binding protein-1c (2007)
  • Author(s): Fujimori K, Aritake K, Urade Y
  • Journal Title: J Biol Chem 282(25) Pages: 18458-66
• [Journal Article] Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid (2007)
  • Author(s): Kanekiyo T, Ban T, Aritake K, Huang ZL, Qu WM, Okazaki I, Mohri I, Murayama S, Ozono K, Taniike M, Goto Y, Urade Y
  • Journal Title: Proc Natl Acad Sci U S A 104(15) Pages: 6412-7
• [Journal Article] NMR solution structure of lipocalin-type prostaglandin D synthase:evidence for partial overlapping of catalytic pocket and retinoic acid-binding pocket within the centralcavity (2007)
  • Author(s): Shimamoto S, et. al.
  • Journal Title: J Biol Chem. 282(43) Pages: 31373-31379
  • Peer Reviewed
• [Journal Article] A novel pathway to enhance adipocyte differentiation of 3T3-L1 cells by up-regulation of lipocalin-type prostaglandin D synthase mediated by liver X receptor-activated sterol regulatory element-binding protein-1c (2007)
  • Author(s): Fujimori K, Aritake K, Urade Y.
  • Journal Title: J Biol Chem. 282(25) Pages: 18458-18466
  • Peer Reviewed
• [Journal Article] Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid (2007)
  • Author(s): Kanekiyo T, et. al.
  • Journal Title: Proc Natl Acad Sci U S A. 104(15) Pages: 6412-6717
  • Peer Reviewed
• [Presentation] リポカリン型PGD合成酵素のPGD2の輸送と結合に関する解析 (2008)
  • Author(s): 有竹浩介
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸国際会議場,神戸国際展示場,神戸ポートピアホテル)
  • Year and Date: 2008-12-12
• [Presentation] リポカリン型PGD合成酵素のPGD_2の輸送と結合に関する解析 (2008)
  • Author(s): 有竹浩介
  • Organizer: 第81回日本生化学会大会
  • Place of Presentation: 神戸ポートアイランド(神戸国際会議場,神戸国際展示場,神戸ポートピアホテル)
  • Year and Date: 2008-12-12
• [Presentation] Lipocalin-type prostaglandin D synthase is a transporter and a scavenger of prostaglandin D2 (2008)
  • Author(s): 有竹浩介
  • Organizer: 33rdFEBS Congress&11th IUBMB Conference
  • Place of Presentation: アテネ
  • Year and Date: 2008-07-03
• [Presentation] Lipocalin-type prostaglandin D synthase is a transporter and a scavenger of prostaglandin D_2 (2008)
  • Author(s): Kosuke Aritake
  • Organizer: 33^<rd>FEBS Congress&11^<th> IUBMB Conference
  • Place of Presentation: アテネ
  • Year and Date: 2008-07-03
• [Presentation] リポカリン型プロスタグランジンD合成酵素における構造学的および生化学的解析 (2007)
  • Author(s): 鶴村俊治
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-14
• [Presentation] リポカリン型プロスタグランジンD合成酵素の輸送蛋白としての機能について (2007)
  • Author(s): 裏出良博
  • Organizer: 第80回日本生化学会大会
  • Place of Presentation: パシフィコ横浜
  • Year and Date: 2007-12-13
• [Book] Multifunctional properties of lipocalin-type prostaglandin D synthase, Prostaglandin D2 Synthase-A Multitude of Biological Functions, 2007, (ed. By Ragolia, L.), (Chapter4) (2007)
  • Author(s): Urade, Y. & Aritake, K
• [Book] PROSTAGLANDIN D2 SYMTHASE-AMULTITUDE OF BIOLOGICAL FUNCTIONS (2007)
  • Author(s): Yoshihiro Urade, Kosuke Aritake
  • Total Pages: 209
  • Publisher: Research Signpost