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Identification of a novel GPCR for oxidized LDL and its role in development of arteriosclerosis.

Research Project

Project/Area Number 22659013
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Biological pharmacy
Research InstitutionTohoku University

Principal Investigator

AOKI Junken  東北大学, 大学院・薬学研究科, 教授 (20250219)

Project Period (FY) 2010 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,090,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2010: ¥1,400,000 (Direct Cost: ¥1,400,000)
Keywords酸化リン脂質 / Gタンパク質共役型受容体 / GPCR / 酸化LDL / リゾホスファチジン酸 / 受容体 / 産生酵素 / ノックアウトマウス
Research Abstract

We identified a novel orphan GPCR that reacted specifically with oxidized phospholipids. In this study we further perform biochemical characterization of the GPCR including precise ligand specificity. In addition, we also examine the patho-physiological roles of the GPCR, especially in the development of arteriosclerosis.

Report

(3 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • Research Products

    (50 results)

All 2012 2011 2010 Other

All Journal Article (30 results) (of which Peer Reviewed: 30 results) Presentation (15 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Synthetic biotinylated peptide compounds derived from Asp-hemolysin : Novel potent inhibitors of platelet-activating factor2012

    • Author(s)
      Sato A, Kumagai T, Aoki J, Ebina K
    • Journal Title

      Eur J Pharmacol

      Volume: 685 Issue: 1-3 Pages: 205-212

    • DOI

      10.1016/j.ejphar.2012.04.025

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Simultaneous quantitation of sphingoid bases and their phosphates in biological samples by liquid chromatography/electrospray ionization tandem mass spectrometry2012

    • Author(s)
      Saigusa D, Shiba K, Inoue A, Hama K, Okutani M, Iida N, Saito M, Suzuki K, Kaneko T, Suzuki N, Yamaguchi H, Mano N, Goto J, Hishinuma T, Aoki J, Tomioka Y
    • Journal Title

      Anal Bioanal Chem

      Volume: 403 Issue: 7 Pages: 1897

    • DOI

      10.1007/s00216-012-6004-9

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The β9 Loop Domain of PA-PLA(1)α Has a Crucial Role in Autosomal Recessive Woolly Hair/Hypotrichosis2012

    • Author(s)
      Shinkuma S, Inoue A, Aoki J, Nishie W, Natsuga K, Ujiie H, Nomura T, Abe R, Akiyama M, Shimizu H
    • Journal Title

      The Journal of Investigative Dermatology

      Volume: (印刷中) Issue: 8 Pages: 2093-2095

    • DOI

      10.1038/jid.2012.96

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] The sphingosine-1-phosphate transporter Spns2 expressed on endothelial cells regulates lymphocyte trafficking in mice2012

    • Author(s)
      Fukuhara S, et al
    • Journal Title

      J Clin Invest

      Volume: (In press)(未定) Issue: 4 Pages: 1416-1426

    • DOI

      10.1172/jci60746

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] GPR34 is a receptor for lysophosphatidylserine with a fatty acid at the sn-2 position2012

    • Author(s)
      Kitamura H, Makide K, Shuto A, Ikubo M, Inoue A, Suzuki K, Sato Y, Nakamura S, Otani Y, Ohwada T, Aoki J
    • Journal Title

      J Biochem

      Volume: 151 Issue: 5 Pages: 511-518

    • DOI

      10.1093/jb/mvs011

    • NAID

      10031166091

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A 3D view of autotaxin2012

    • Author(s)
      Nishimasu H, Ishitani R, Aoki J, Nureki O
    • Journal Title

      Trends Pharmacol Sci

      Volume: 33 Issue: 3 Pages: 138-145

    • DOI

      10.1016/j.tips.2011.12.004

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Surface loops of extracellular phospholipase A(1) determine both substrate specificity and preference for lysophospholipids2012

    • Author(s)
      Arima N, Inoue A., et al
    • Journal Title

      J Lipid Res

      Volume: 53 Issue: 3 Pages: 513-521

    • DOI

      10.1194/jlr.m022400

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of peroxisomal lipid metabolism by catalytic activity of tumor suppressor H-rev1072012

    • Author(s)
      Uyama T, Ichi I, Kono N, Inoue A, Tsuboi K, Jin XH, Araki N, Aoki J, Arai H, Ueda N
    • Journal Title

      J Biol Chem

      Volume: 287 Issue: 4 Pages: 2706

    • DOI

      10.1074/jbc.m111.267575

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification and biochemical characterization of a novel autotaxin isoform, ATXδ, with a four-amino acid deletion2012

    • Author(s)
      Hashimoto T, Okudaira S, Igarashi K, Hama K, Yatomi Y, Aoki J
    • Journal Title

      J Biochem

      Volume: 151 Issue: 1 Pages: 89

    • DOI

      10.1093/jb/mvr126

    • NAID

      10031166046

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autotaxin regulates vascular development via multiple lysophosphatidic acid (LPA) receptors in zebrafish2011

    • Author(s)
      Yukiura H, Hama K, Nakanaga K, Tanaka M, Asaoka Y, Okudaira S, Arima N, Inoue A, Hashimoto T, Arai H, Kawahara A, Nishina H, Aoki J
    • Journal Title

      J Biol Chem

      Volume: 286 Issue: 51 Pages: 43972

    • DOI

      10.1074/jbc.m111.301093

    • Related Report
      2011 Annual Research Report 2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] LPA-producing enzyme PA-PLA <sub>1</sub> α regulates hair follicle development by modulating EGFR signalling2011

    • Author(s)
      Inoue A., Arima N., et al
    • Journal Title

      EMBO J

      Volume: 30 Issue: 20 Pages: 4248

    • DOI

      10.1038/emboj.2011.296

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Serum autotaxin measurements in pregnant women : application for the differentiation of normal pregnancy and pregnancy-induced hypertension2011

    • Author(s)
      Masuda A, Fujii T, Iwasawa Y, Nakamura K, Ohkawa R, Igarashi K, Okudaira S, Ikeda H, Kozuma S, Aoki J, Yatomi Y
    • Journal Title

      Clin Chim Acta

      Volume: 412 Issue: 21-22 Pages: 1944-1950

    • DOI

      10.1016/j.cca.2011.06.039

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Fluorescence Probe for Lysophospholipase C/NPP6 Activity and a Potent NPP6 Inhibitor2011

    • Author(s)
      Mitsuyasu Kawaguchi, Takayoshi Okabe, Shinichi, Okudaira, Kenjiro Hanaoka, Yuuta Fujikawa, Takuya Terai, Toru Komatsu, Hirotatsu Kojima, Junken Aoki, Tetsuo Nagano
    • Journal Title

      Journal of the American Chemical Society

      Volume: 133 Issue: 31 Pages: 12021-12030

    • DOI

      10.1021/ja201028t

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Specific increase in serum autotaxin activity in patients with pancreatic cancer2011

    • Author(s)
      Nakai Y, Ikeda H, Nakamura K, Kume Y, Fujishiro M, Sasahira N, Hirano K, Isayama H, Tada M, Kawabe T, Komatsu Y, Omata M, Aoki J, Koike K, Yatomi Y
    • Journal Title

      Clin Biochem

      Volume: 44 Issue: 8-9 Pages: 576-581

    • DOI

      10.1016/j.clinbiochem.2011.03.128

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autotaxin as a novel serum marker of liver fibrosis2011

    • Author(s)
      Nakagawa H, Ikeda H, Nakamura K, Ohkawa R, Masuzaki R, Tateishi R, Yoshida H, Watanabe N, Tejima K, Kume Y, Iwai T, Suzuki A, Tomiya T, Inoue Y, Nishikawa T, Ohtomo N, Tanoue Y, Omata M, Igarashi K, Aoki J, Koike K, Yatomi Y
    • Journal Title

      Clin Chim Acta

      Volume: 412 Issue: 13-14 Pages: 1201-1206

    • DOI

      10.1016/j.cca.2011.03.014

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Crystal structure of autotaxin and insight into GPCR activation by lipid mediators2011

    • Author(s)
      Nishimasu H, Okudaira S, Hama K, Mihara E, Dohmae N, Inoue A, Ishitani R, Takagi J, Aoki J, Nureki O
    • Journal Title

      Nat Struct Mol Biol

      Volume: 18 Issue: 2 Pages: 205

    • DOI

      10.1038/nsmb.1998

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Immunohistochemical detection of autotaxin (ATX)/lysophospholipase D (lysoPLD)in submucosal invasive colorectal cancer2011

    • Author(s)
      Kazama S, Kitayama J, Aoki J, Mori K, Nagawa H.
    • Journal Title

      J Gastrointest Cancer

      Volume: 42 Pages: 204-211

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autotaxin and lysophosphatidic acid1 receptor-mediated demyelination of dorsal root fibers by sciatic nerve injury and intrathecal lysophosphatidylcholine2010

    • Author(s)
      Nagai J, Uchida H, Matsushita Y, Yano R, Ueda M, Niwa M, Aoki J, Chun J, Ueda H
    • Journal Title

      Mol Pain

      Volume: 6 Pages: 78-78

    • DOI

      10.1186/1744-8069-6-78

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Development of an activity-based probe for autotaxin2010

    • Author(s)
      Cavalli S, Houben AJ, Albers HM, van Tilburg EW, de Ru A, Aoki J, van Veelen P, Moolenaar WH, Ovaa H
    • Journal Title

      Chembiochem

      Volume: 11 Issue: 16 Pages: 2311-2317

    • DOI

      10.1002/cbic.201000349

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autotaxin controls caudal diencephalon-mesencephalon development in the chick2010

    • Author(s)
      Ohuchi H, Fukui H, Matsuyo A, Tomonari S, Tanaka M, Arai H, Noji S, Aoki J
    • Journal Title

      Dev Dyn

      Volume: 239 Issue: 10 Pages: 2647

    • DOI

      10.1002/dvdy.22403

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Expression of phosphatidylserine-specific phospholipase A(1)mRNA in human THP-1-derived macrophages2010

    • Author(s)
      Hosono H, Homma M, Ogasawara Y, Makide K, Aoki J, Niwata H, Watanabe M, Inoue K, Ohkohchi N, Kohda Y
    • Journal Title

      Cell Transplant

      Volume: 19 Pages: 759-64

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Glucagon regulates intracellular distribution of adipose differentiation-related protein during triacylglycerol accumulation in the liver2010

    • Author(s)
      Takahashi K, Sasabe N, Ohshima K, Kitazato K, Kato R, Masuda Y, Tsurumaki M, Obama T, Okudaira S, Aoki J, Arai H, Yamaguchi T, Itabe H
    • Journal Title

      J Lipid Res

      Volume: 51 Issue: 9 Pages: 2571

    • DOI

      10.1194/jlr.m004648

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Autotaxin-An LPA producing enzyme with diverse functions2010

    • Author(s)
      Nakanaga K, Hama K, Aoki J
    • Journal Title

      J Biochem

      Volume: 148 Issue: 1 Pages: 13

    • DOI

      10.1093/jb/mvq052

    • NAID

      10027876904

    • URL

      https://pure.teikyo.jp/en/publications/cea86bdd-201e-419f-8268-1cd456e47e51

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Biological roles of lysophosphatidic acid signaling through its production by autotaxin2010

    • Author(s)
      Okudaira S, Yukiura H, Aoki J
    • Journal Title

      Biochimie

      Volume: 92 Issue: 6 Pages: 698-706

    • DOI

      10.1016/j.biochi.2010.04.015

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel enzyme immunoassay for the determination of phosphatidylserine-specific phospholipase A<sub>1</sub> in human serum samples2010

    • Author(s)
      Nakamura K, Igarashi K, Ohkawa R, Saiki N, Nagasaki M, Uno K, Hayashi N, Sawada T, Syukuya K, Yokota H, Arai H, Ikeda H, Aoki J, Yatomi Y
    • Journal Title

      Clin Chim Acta

      Volume: 411 Issue: 1-16 Pages: 1090

    • DOI

      10.1016/j.cca.2010.04.006

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cancer cell expression of autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts2010

    • Author(s)
      David M, Wannecq E, Descotes F, Jansen S, Deux B, Ribeiro J, Serre CM, Gres S, Bendriss-Vermare N, Bollen M, Saez S, Aoki J, Saulnier-Blache JS, Clezardin P, Peyruchaud O
    • Journal Title

      PLoS One

      Volume: 17 Issue: 3 Pages: e9741-e9741

    • DOI

      10.1371/journal.pone.0009741

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] LPA<sub>3</sub>, a unique G protein-coupled receptor for lysophosphatidic acid2010

    • Author(s)
      Hama K, Aoki J
    • Journal Title

      Prog Lipid Res

      Volume: 49 Issue: 4 Pages: 335

    • DOI

      10.1016/j.plipres.2010.03.001

    • URL

      https://pure.teikyo.jp/en/publications/2ee6ad5f-3aea-46c9-81b2-0bc25a80b051

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Prevalent LIPH founder mutations lead to loss of P2Y5 activation ability of PA-PLA1alpha in autosomal recessive hypotrichosis2010

    • Author(s)
      Shinkuma S, Akiyama M, Inoue A, Aoki J, Natsuga K, Nomura T, Arita K, Abe R, Ito K, Nakamura H, Ujiie H, Shibaki A, Suga H, Tsunemi Y, Nishie W, Shimizu H
    • Journal Title

      Hum Mutat

      Volume: 31 Pages: 602-10

    • DOI

      10.1002/humu.21235

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Evidence for de novo synthesis of lysophosphatidic acid in the spinal cord through phospholipase A2 and autotaxin in nerve injury-induced neuropathic pain2010

    • Author(s)
      Ma L, Uchida H, Nagai J, Inoue M, Aoki J, Ueda H
    • Journal Title

      J Pharmacol Exp Ther

      Volume: 333 Issue: 2 Pages: 540-546

    • DOI

      10.1124/jpet.109.164830

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Adiponectin suppresses tumorigenesis in Apc(Min)(/+)mice2010

    • Author(s)
      Otani K, Kitayama J, Yasuda K, Nio Y, Iwabu M, Okudaira S, Aoki J, Yamauchi T, Kadowaki T, Nagawa H
    • Journal Title

      Cancer Lett

      Volume: 288 Issue: 2 Pages: 177-82

    • DOI

      10.1016/j.canlet.2009.06.037

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Presentation] 酸化リン脂質に応答する新規受容体の同定2012

    • Author(s)
      石黒純
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      札幌
    • Year and Date
      2012-03-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Ectodomain shedding of TGFα as a versatile readout for GPCR activation2012

    • Author(s)
      Asuka Inoue, 他
    • Organizer
      Keystone Symposia G Protein-Coupled Receptors : Molecular Mechanisms and Novel Functional Insights
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2012-02-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] Development and characterization of TGFalpha shedding assay : a novel and powerful method to detect G12/13 signaling2012

    • Author(s)
      Jun Ishiguro, 他
    • Organizer
      Keystone Symposia G Protein-Coupled Receptors : Molecular Mechanisms and Novel Functional Insights
    • Place of Presentation
      Banff, Canada
    • Year and Date
      2012-02-17
    • Related Report
      2011 Annual Research Report
  • [Presentation] 生理活性リゾリン脂質の定量系の開発と産生機構の解析2011

    • Author(s)
      井上飛鳥, 他
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] 新規GPCRシグナル検出法~TGFalpha切断アッセイ~の開発2011

    • Author(s)
      石黒純, 他
    • Organizer
      第84回日本生化学会大会
    • Place of Presentation
      京都
    • Year and Date
      2011-09-21
    • Related Report
      2011 Annual Research Report
  • [Presentation] Autotaxin regulates vascular development via multiple LPA receptors in zebrafish2011

    • Author(s)
      Junken Aoki
    • Organizer
      2011 FASEB Summer Research Conference
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      2011-08-15
    • Related Report
      2011 Final Research Report
  • [Presentation] TGF-alpha ectodomain shedding underlies LPA-induced hair formation2011

    • Author(s)
      Asuka Inoue, 他
    • Organizer
      2011 FASEB Summer Research Conference
    • Place of Presentation
      Lucca, Italy
    • Year and Date
      2011-08-14
    • Related Report
      2011 Annual Research Report
  • [Presentation] Mechanism of extracellular production of bioactive lysophospholipids using a newly developed LC-MS/MS method2011

    • Author(s)
      Asuka Inoue, 他
    • Organizer
      LIPID MAPS Annual Meeting 2011
    • Place of Presentation
      San Diego, USA
    • Year and Date
      2011-05-02
    • Related Report
      2011 Annual Research Report
  • [Presentation] TGFα切断アッセイを用いたオーファンGPCRのリガンドスクリーニング2010

    • Author(s)
      石黒純
    • Organizer
      第9回次世代を担う若手ファーマ・バイオフ_オーラム2010
    • Place of Presentation
      京都、京都大学大学院薬学研究科
    • Year and Date
      2010-10-02
    • Related Report
      2010 Annual Research Report
  • [Presentation] Lysophosphatidic acid plays a critical role in hair follicle formation through TGF.-alpha release and EGFR transactivation2010

    • Author(s)
      井上飛鳥
    • Organizer
      The 27th Naito Conference on Menmbrane Dynamics and Lipid Biology[I]
    • Place of Presentation
      Sapporo,CHATERAISE Gateaux Kingdom SAPPORO
    • Year and Date
      2010-06-29
    • Related Report
      2010 Annual Research Report
  • [Presentation] TGFα切断アッセイによるGPCRシグナルの検出2010

    • Author(s)
      石黒純
    • Organizer
      第52回日本脂質生化学会
    • Place of Presentation
      群馬、秋森旅館
    • Year and Date
      2010-06-15
    • Related Report
      2010 Annual Research Report
  • [Presentation] Autotaxin and LPA Signaling in Cardiovascular Development2010

    • Author(s)
      Junken Aoki
    • Organizer
      Keystone Symposia
    • Place of Presentation
      Kyoto, Japan
    • Year and Date
      2010-06-08
    • Related Report
      2011 Final Research Report
  • [Presentation] Lysophosphatidic acid plays a critical role in hair follicle formation through TGFa release and EGFR transactivation2010

    • Author(s)
      井上飛鳥
    • Organizer
      Keystone Symposia Bioactive Lipids : Biochemistry and Diseases(D2)
    • Place of Presentation
      Kyoto, Westin Miyako Kyoto
    • Year and Date
      2010-06-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] TGFα切断アッセイによるG12/13シグナルの検出2010

    • Author(s)
      石黒純
    • Organizer
      第7回GPCR研究会
    • Place of Presentation
      東京、日本科学未来館 みらいCANホール
    • Year and Date
      2010-05-07
    • Related Report
      2010 Annual Research Report
  • [Presentation] 新規GPCRシグナル検出法-TGFα切断アッセイ・の開発2010

    • Author(s)
      石黒純
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡、静岡県コンベンションアーツセンター
    • Year and Date
      2010-03-28
    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www.pharm.tohoku.ac.jp/~seika/H21/index.html

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://www.pharm.tohoku.ac.jp/~seika/H21/index.html

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] オートタキシンアイソフォーム特異的抗体および検出方法2011

    • Inventor(s)
      青木淳賢、五十嵐浩二
    • Industrial Property Rights Holder
      株式会社東ソー、東北大学
    • Industrial Property Number
      2011-150054
    • Filing Date
      2011-07-06
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 自己免疫疾患治療薬のスクリーニング方法2011

    • Inventor(s)
      青木淳賢、巻出久美子、井上飛鳥、大和田智彦、井久保仁也、尾谷優子
    • Industrial Property Rights Holder
      東北大学、東京大学
    • Industrial Property Number
      2011-112881
    • Filing Date
      2011-05-29
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] ホスファチジルセリン特異的ホスホリパーゼA1測定による全身性エリテマトーデスの検査方法および検査薬2010

    • Inventor(s)
      沢田哲治、矢冨裕、中村和宏、青木淳賢、五十嵐浩二
    • Industrial Property Rights Holder
      株式会社東ソー、東京大学、東北大学
    • Industrial Property Number
      2010-172068
    • Filing Date
      2010-07-30
    • Related Report
      2011 Final Research Report

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Published: 2010-08-23   Modified: 2016-04-21  

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