Patho-physiological role of bioactive lysophospholipids

• Project/Area Number: 19390018
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biological pharmacy
• Research Institution: Tohoku University
• Principal Investigator: AOKI Junken Tohoku University, 大学院・薬学研究科, 教授 (20250219)
• Project Period (FY): 2007 – 2008
• Project Status: Completed (Fiscal Year 2008)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2008: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000); Fiscal Year 2007: ¥12,090,000 (Direct Cost: ¥9,300,000、Indirect Cost: ¥2,790,000)
• Keywords: リゾホスファチジン酸 / リゾホスファチジルセリン / 受容体 / 産生酵素 / ノックアウトマウス

Research Abstract

リゾリン脂質の新規生理機能の解明を行い、リゾホスファチジン酸(LPA)が新たなLPA受容体を介し内皮細胞の接着を負に制御することを見いだし、LPAの内皮細胞制御の新たなメカニズムを提唱した。また、新規リゾホスファチジルセリン(LPS)受容体GPR34が未熟マスト細胞に発現し、未熟マスト細胞のカルシウム応答に関与すること、GPR34発現細胞はLPSに対して走化性を示すことを見いだした。

Research Products

• [Journal Article] Lysophospliolipid mediators (2009)
  • Author(s): Makide K, Kano K, Kitamura H, Arima N, Aoki J.
  • Journal Title: Tanpakushitsu Kakusan Koso 54 Pages: 29-39
• [Journal Article] Protection against oxidative stress-induced hepatic injury by intracellular type II PAF-acetylhydrolase by metabolism of oxidized phospholipids in vivo (2009)
  • Author(s): Nakamura, K., Igarashi, K., Ohkawa, R., Okubo, S., Yokota, H., Kishimoto, T., Ide, K., Masuda, A., Yamamoto, T., Saito, N., Kurokawa, M., Tsuji, S., Okudaira, S., Ikeda, H., Aoki, J., and Yatomi, Y.
  • Journal Title: J. Biol. Chem. (In press)
  • Peer Reviewed
• [Journal Article] Analysis of serum and urinary lysophospholipase D/autotaxin in nephrotic syndrome (2009)
  • Author(s): Makide, K., Kitamura, H., Sato, Y., Okutani, M., and Aoki, J.
  • Journal Title: POLM (In press)
  • Peer Reviewed
• [Journal Article] Embryo Spacing and Implantation Timing Are Differentially Regulated by LPA3-Mediated Lysophosphatidic Acid Signaling in Mice (2009)
  • Author(s): Endo, T., Kano, K., Motoki, R., Hama, K., Okudaira, S., Ishida, M., Ogiso, H., Tanaka, M., Matsuki, N., Taguchi, R., Kanai, M., Shibasaki, M., Arai, H., and Aoki. J.
  • Journal Title: J. Biochem (In press)
  • Peer Reviewed
• [Journal Article] Validation of an autotaxin enzyme immunoassay in human serum samples and its application to hypoalbuminemia differentiation (2008)
  • Author(s): Nakamura, K., K. Igarashi, K. Ide, R. Ohkawa, S. Okubo, H. Yokota, A. Masuda, N. Oshima, T. Takeuchi, M. Nangaku, S. Okudaira, H. Arai, H. Ikeda, Aoki J,and Y. Yatomi
  • Journal Title: Clin.Chim.Acta. 388 Pages: 51-8
  • Peer Reviewed
• [Journal Article] Simultaneous stimulation of spinal NK1 and NMDA receptors produces LPC which undergoes ATX-mediated conversion to LPA,an initiator of neuropathic pain (2008)
  • Author(s): Inoue M, Ma L, Aoki J, Ueda H.
  • Journal Title: J Neurochem. 107 Pages: 1556-1565
  • Peer Reviewed
• [Journal Article] Expression patterns of the lysophospholipid receptor genes during mouse early development (2008)
  • Author(s): Ohuchi H, Hamada A, Matsuda H, Takagi A, Tanaka M, Aoki J, Arai H, Noji S.
  • Journal Title: Dev Dyn. 237 Pages: 3280-3294
  • Peer Reviewed
• [Journal Article] Involvement of the Lysophosphatidic Acid-Generating Enzyme Autotaxin in Lymphocyte-Endothelial Cell Interactions Am (2008)
  • Author(s): Nakasaki T, Tanaka T, Okudaira S, Hirosawa M, Umemoto E, Otani K, Jin S, Bai Z, Hayasaka H, Fukui Y, Aozasa K, Fujita N, Tsuruo T, Ozono K, Aoki J and Miyasaka M
  • Journal Title: J. Pathol 237 Pages: 3280-3294
  • Peer Reviewed
• [Journal Article] LPA and its analogs-attractive tools for elucidation of LPA biology and drug development(review) (2008)
  • Author(s): Kano K, Arima N, Ohgami M, and Aoki J
  • Journal Title: Curr.Med.Chem. 15 Pages: 2122-2131
  • Peer Reviewed
• [Journal Article] Serum autotaxin measurement in haematological malignancies : a promising marker for follicular lymphoma (2008)
  • Author(s): Masuda A, Nakamura K, Izutsu K, Igarashi K, Ohkawa R, Jona M, Higashi K, Yokota H, Okudaira S, Kishimoto T, Watanabe T, Koike Y, Ikeda H, Kozai Y, Kurokawa M, Aoki J, Yatomi Y
  • Journal Title: Br J Haematol 143 Pages: 60-70
  • Peer Reviewed
• [Journal Article] Two pathways for lysophosphatidic acid production(review) (2008)
  • Author(s): Aoki J, Inoue A,and Okudaira S.
  • Journal Title: Biochim.Biophys.Acta. 1781 Pages: 513-518
  • Peer Reviewed
• [Journal Article] Beta-catenin asymmetry is regulated by PLA1 and retrograde traffic in C. elegans stem cell divisions (2008)
  • Author(s): Kanamori T, Inoue T, Sakamoto T, Gengyo-Ando K, Tsujimoto M, Mitani S, Sawa H, Aoki J, and Arai H.
  • Journal Title: EMBO J. 27 Pages: 1647-1657
  • Peer Reviewed
• [Journal Article] Autotaxin, a synthetic enzyme of lysophosphatidic acid(LPA), mediates the induction of nerve-injured neuropathic pain (2008)
  • Author(s): Inoue M, Ma L, Aoki J, Chun J, Ueda H.
  • Journal Title: Mol Pain 4 Pages: 6-6
  • NAID: 120006982424
  • Peer Reviewed
• [Journal Article] Analysis of serum and urinary lysophospholipase D/autotaxin in nephrotic syndrome (2008)
  • Author(s): Nakamura K, Nangaku M, Ohkawa R, Okubo S, Yokota H, Ikeda H, Aoki J, Yatomi Y
  • Journal Title: Clin Chem Lab Med. 46 Pages: 150-151
  • Peer Reviewed
• [Journal Article] Validation of an autotaxin enzyme immunoassay in human serum samples and its application to hypoalbuminemia differentiation (2008)
  • Author(s): Nakamura K, Igarashi K, Ide K, Ohkawa R, Okubo S, Yokota H, Masuda A, Oshima N, Takeuchi T, Nangaku M, Okudaira S, Arai H, Ikeda H, Aoki J, Yatomi Y
  • Journal Title: Clin Chim Acta 388 Pages: 51-58
  • Peer Reviewed
• [Journal Article] Protection against oxidative stress-induced hepatic injury by intracellular type II platelet-activating factor acetylhydrolase by metabolism of oxidized phospholipids in vivo (2008)
  • Author(s): Kono N, Inoue T, Yoshida Y, Sato H, Matsusue T, Itabe H, Niki E, Aoki J, Arai H
  • Journal Title: J.Biol.Chem. 283 Pages: 1628-1636
  • Peer Reviewed
• [Journal Article] Validation of an autotaxin enzyme immunoassay in human serum samples and its application to hypoalbuminemia differentiation (2008)
  • Author(s): Makide, K., Kano, K., Kitamura, H., Arima. N.. and Aoki. J.
  • Journal Title: Tanpakushitsu Kakusan Koso 54 Pages: 29-39
• [Journal Article] Phospholipase A (1) assays using a radiolabeled substrate and mass spectrometry (2008)
  • Author(s): Ohuchi, H., Hamada, A., Matsuda, H., Takagi, A., Tanaka, M., Aoki, J., Arai, H., and Noii, S.
  • Journal Title: Dev. Dyn. 237 Pages: 3280-3294
  • Peer Reviewed
• [Journal Article] Serum lysophospholipase D/autotaxin may be a new nutritional assessment marker : study on prostate cancer patients (2008)
  • Author(s): Nakasaki, T., Tanaka, T., Okudaira, S., Hirosawa, M., Umemoto, E., Otani, K., Jin, S., Bai, Z., Hayasaka, H., Fukui, Y, Aozasa, K., Fujita, N., Tsuruo, T., Ozono, K., Aoki, J., and Miyasaka, M.
  • Journal Title: Am J Pathol 173 Pages: 1566-1576
  • Peer Reviewed
• [Journal Article] Protection against oxidative stress-induced hepatic injury by intracellular type IIPAF-acetylhydrolase by metabolism of oxidized phospholipids in vivo. (2008)
  • Author(s): Kono N, Inoue T, Yoshida Y, Sato H, Matsusue T, Itabe H, Niki E, Aoki J, Arai H.
  • Journal Title: J. Biol. Chem. 283 Pages: 1628-1636
  • Peer Reviewed
• [Journal Article] Analysis of serum and urinary lysophospholipase D/autotaxin in nephrotic syndrome. (2008)
  • Author(s): Nakamura K, Nangaku M, Ohkawa R, Okubo S, Yokota H, Ikeda H, Aoki J, Yatomi Y.
  • Journal Title: Clin. Chem. Lab. Med. 46 Pages: 150-151
  • Peer Reviewed
• [Journal Article] Validation of an autotaxin enzyme immunoassay in human serum samples and itsapplication to hypoalbuminemia differentiation. (2008)
  • Author(s): Nakamura K, Igarashi K, Ide K, Ohkawa R, Okubo S, Yokota H, Masuda A, Oshima N, Takeuchi T, Nangaku M, Okudaira S, Arai H, Ikeda H, Aoki J, Yatomi Y.
  • Journal Title: Clin. Chim. Acta 388 Pages: 51-58
  • Peer Reviewed
• [Journal Article] Phospholipase A1-structure, distribution and function- (2007)
  • Author(s): Inoue, A.,and Aoki, J.
  • Journal Title: Future Lipidology 1 Pages: 699-700
  • Peer Reviewed
• [Journal Article] Embryo Spacing and Implantation Timing Are Differentially Regulated by LPA3-Mediated Lysophosphatidic Acid Signaling in Mice (2007)
  • Author(s): Hama, K., Aoki J., A. Inoue, T. Endo, T. Amano, R. Motoki, M. Kanai, X. Ye, J. Chun, N. Matsuki, H. Suzuki, M. Shibasaki,and H. Arai
  • Journal Title: Biol.Reprod 77 Pages: 954-959
  • Peer Reviewed
• [Journal Article] Structure and function of extracellular phospholipase A(1) belonging to the pancreatic lipase gene family (2007)
  • Author(s): Aoki, J., A. Inoue, K. Makide, N. Saiki,and H. Arai
  • Journal Title: Biochimie 89 Pages: 197-204
  • Peer Reviewed
• [Journal Article] Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid(LPA)in the gastrointestinal tract through the secretion of autotaxin(ATX)/lysophospholipase D(lysoPLD) (2007)
  • Author(s): Mori, K., J. Kitayama, Aoki, J. Y. Kishi, D. Shida, H. Yamashita, H. Arai,and H. Nagawa
  • Journal Title: Virchows Arch. 451 Pages: 47-56
  • Peer Reviewed
• [Journal Article] Phospholipase A(1) assays using a radiolabeled substrate and mass spectrometry (2007)
  • Author(s): Morikawa, R., M. Tsujimoto, H. Arai,and Aoki J.
  • Journal Title: Methods Enzymol 434 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Diversified expression patterns of autotaxin, a gene for phospholipid-generating enzyme during mouse and chicken development (2007)
  • Author(s): Ohuchi, H., Y. Hayashibaral, H. Matsuda, M. Onoi, M. Mitsumori, M. Tanaka, Aoki J, H. Arai,and S. Noji
  • Journal Title: Dev.Dyn. 236 Pages: 1134-1143
  • Peer Reviewed
• [Journal Article] Embryo Spacing and Implantation Timing Are Differentially Regulated by LPA3-Mediated Lysophosphatidic Acid Signaling in Mice. (2007)
  • Author(s): Hama K, Aoki J, Inoue A, Endo T, Amano T, Motoki R, Kanai M, Ye X, Chun J, Matsuki N, Suzuki H, Shibasaki M, Arai H.
  • Journal Title: Biol. Reprod. 77 Pages: 954-959
  • Peer Reviewed
• [Journal Article] Phospholipase A(1)assays using a radiolabeled substrate and mass spectrometry. (2007)
  • Author(s): Morikawa R, Tsujimoto M, Arai H, Aoki J.
  • Journal Title: Methods Enzymol. 434 Pages: 1-13
  • Peer Reviewed
• [Journal Article] Serum lysophospholipase D/autotaxin may be a new nutritional assessment marker: study on prostate cancer patients. (2007)
  • Author(s): Nakamura K, Takeuchi T, Ohkawa R, Okubo S, Yokota H, Tozuka M, Aoki J, Arai H, Ikeda H, Ohshima N, Kitamura T, Yatomi Y.
  • Journal Title: Ann. Clin. Biochem. 44 Pages: 549-556
  • Peer Reviewed
• [Journal Article] Type I platelet-activating factor acetylhydrolase catalytic subunits over-expression induces pleiomorphic nuclei and centrosome amplification. (2007)
  • Author(s): Yamaguchi N, Koizumi H, Aoki J, Natori Y, Nishikawa K, Natori Y, Takanezawa Y, Arai H.
  • Journal Title: Genes Cells 12 Pages: 1153-1161
  • Peer Reviewed
• [Journal Article] Plasma lysophosphatidic acid level and serum autotaxin activity are increased in liverinjury in rats in relation to its severity. (2007)
  • Author(s): Watanabe N, Ikeda H, Nakamura K, Ohkawa R, Kume Y, Tomiya T, Tejima K, Nishikawa T, Arai M, Yanase M, Aoki J, Arai H, Omata M, Fujiwara K, Yatomi Y.
  • Journal Title: Life Sci. 81 Pages: 1009-1015
  • Peer Reviewed
• [Journal Article] Submucosal connective tissue-type mast cells contribute to the production of lysophosphatidic acid(LPA)in the gastrointestinal tract through the secretion of autotaxin(ATX)/lysophospholipase D(lysoPLD). (2007)
  • Author(s): Mori K, Kitayama J, Aoki J, Kishi Y, Shida D, Yamashita H, Arai H, Nagawa H.
  • Journal Title: Virchows Arch. 451 Pages: 47-56
  • Peer Reviewed
• [Journal Article] Lysophosphatidic acid protection against apoptosis in the human pre-B-cell line Nalm-6. (2007)
  • Author(s): Satoh Y, Ohkawa R, Nakamura K, Higashi K, Kaneko M, Yokota H, Aoki J, Arai H, Yuasa Y, Yatomi Y.
  • Journal Title: Eur. J. Haematol. 78 Pages: 510-517
  • Peer Reviewed
• [Journal Article] Diversified expression patterns of autotaxin, a gene for phospholipid-generating enzymeduring mouse and chicken development. (2007)
  • Author(s): Ohuchi H, Hayashibara Y, Matsuda H, Onoi M, Mitsumori M, Tanaka M, Aoki J, Arai H, Noji S.
  • Journal Title: Dev. Dyn. 236 Pages: 1134-1143
  • Peer Reviewed
• [Journal Article] Peritoneal fluids from patients with certain gynecologic tumor contain elevated levels ofbioactive lysophospholipase D activi (2007)
  • Author(s): Tokumura A, Kume T, Fukuzawa K, Tahara M, Tasaka K, Aoki J, Arai H
  • Journal Title: Life Sci. 80 Pages: 1641-1649
  • Peer Reviewed
• [Journal Article] Neuroprotective Role of Transgenic PAF-Acetylhydrolase II in Mouse Models of Focal Cerebral Ischemia. (2007)
  • Author(s): Umemura K, Kato I, Hirashima Y, Ishii Y, Inoue T, Aoki J, Kono N, Oya T, Hayashi N, Hamada H, Endo S, Oda M, Arai H, Kinouchi H, Hiraga K.
  • Journal Title: Stroke 38 Pages: 1036-1068
  • Peer Reviewed
• [Journal Article] Plasma lysophosphatidic acid is increased in liver fibrosis in rats and human with enhanced serum autotaxin level. (2007)
  • Author(s): Watanabe N, Ikeda H, Nakamura K, Ohkawa R, Kume Y, Aoki J, Hama K, Okudaira S, Tanaka M, Yanase M, Nagashima K, Tomiya T, Arai M, Inoue Y, Tejima K, Nishikawa T, Arai H, Omata M, Fujiwara K, Yatomi Y
  • Journal Title: J. Clin. Gastroenterol 41 Pages: 616-623
  • Peer Reviewed
• [Journal Article] Structure and function of extracellular phospholipase Al belonging to the pancreatic lipase gene family(review). (2007)
  • Author(s): AokiJ, Inoue A, Makide K, Saiki N, Arai H.
  • Journal Title: Biochimie 89 Pages: 197-204
  • Peer Reviewed
• [Journal Article] Measurement of lysophospholipase D/autotaxin activity in human serum samples (2007)
  • Author(s): Nakamura K, Ohkawa R, Okubo S, Tozuka M, Okada M, Aoki S, Aoki J, Arai H, Ikeda H, Yatomi Y
  • Journal Title: Clin. Biochem. 40 Pages: 274-277
  • Peer Reviewed
• [Journal Article] Autotaxin(NPP-2)in the brain: Cell type-specific expression and regulation during development and after neurotrauma (2007)
  • Author(s): Savaskan NE, Rocha L, Kotter MR, Lubec G, Baer A, van Meeteren LA, Kishi Y, Aoki J, Moolenaar WH, Nitsch R, Brauer AU.
  • Journal Title: Cell. Mol. Life Sci. 64 Pages: 230-243
  • Peer Reviewed
• [Presentation] 生理活性リゾリン脂質の生体内機能リゾリン脂質メディエーターの生理・病態機能 (2008)
  • Author(s): 青木淳賢
  • Organizer: 第30回東北薬学セミナー(特別講演)
  • Place of Presentation: 仙台、江陽グランドホテル
  • Year and Date: 2008-12-05
• [Presentation] コンディショナルノックアウトマウスを用いたリゾホスファチジン酸産生酵素オートタキシンの機能解析 (2008)
  • Author(s): 大上満、奥平真一、Wouter Moolenaar、新井洋由、青木淳賢
  • Organizer: ファーマ・バイオフォーラム2008
  • Place of Presentation: 東京都、渋谷、日本薬学会長井記念ホール
  • Year and Date: 2008-11-29
• [Presentation] PS-PLA1とmPA-PLA1aの基質特異性におけるループ構造の関与 (2008)
  • Author(s): 有馬直明、井上飛鳥、巻出久美子、青木淳賢
  • Organizer: 第47回日本薬学会東北支部大会
  • Place of Presentation: 岩手, 岩手医科大学薬学部
  • Year and Date: 2008-10-26
• [Presentation] メディエーターとしての生体膜脂質の機能-リゾリン脂質メディエーターの生理・病態機能 (2008)
  • Author(s): 青木淳賢
  • Organizer: 生体パーオキシド研究会特別講演
  • Place of Presentation: 仙台、勝山館
  • Year and Date: 2008-08-30
• [Presentation] 生理活性リゾリン脂質-新しいドラッグターゲット (2008)
  • Author(s): 青木淳賢
  • Organizer: 東北大学バイオシンポジウム
  • Place of Presentation: 東京、サピアタワー
  • Year and Date: 2008-06-06
• [Presentation] 初期炎症反応に生理活性脂質リゾホスファチジン酸の役割 (2008)
  • Author(s): 青木淳賢
  • Organizer: 日本脂質生化学会
  • Place of Presentation: 徳島県徳島市徳島県郷土文化会館
  • Year and Date: 2008-06-05
• [Presentation] ホスファチジン酸特異的ホスホリパーゼAlの体毛形成への関与 (2008)
  • Author(s): 井上飛鳥、有馬直明、新井洋由、青木淳賢
  • Organizer: 日本脂質生化学会
  • Place of Presentation: 徳島県徳島市徳島県郷土文化会館
  • Year and Date: 2008-06-05
• [Presentation] VE-カドヘリンの接着抑制に関わる内皮細胞上のLPA受容体の解析 (2008)
  • Author(s): 中永景太、田中将之、望月直樹、金井求、柴崎正勝、新井洋由、青木淳賢
  • Organizer: BMB2008第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Presentation] リゾホスファチジルセリン受容体GPR34の解析 (2008)
  • Author(s): 巻出久美子、佐藤侑介、北村一、秋山るみ、青木淳賢
  • Organizer: BMB2008第31回日本分子生物学会年会・第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸、神戸ポートアイランド
• [Presentation] リゾホスファチジン酸受容体LPA3の降圧メカニズムの解析 (2008)
  • Author(s): 可野邦行、遠藤智子、池下和樹、長谷川英之、金井浩、Jerold Chun、青木淳賢
  • Organizer: ファーマ・バイオフォーラム2008
  • Place of Presentation: 渋谷、日本薬学会長井記念ホール
• [Presentation] リゾホスファチジン酸産生酵素オートタキシンの初期炎症過程における機能 (2008)
  • Author(s): 青木淳賢、奥平真一、新井洋由
  • Organizer: 第50回日本脂質生化学会
  • Place of Presentation: 徳島、徳島県郷土文化会館
• [Presentation] リゾホスファチジン酸受容体LPA3の新規生理機能 (2008)
  • Author(s): 青木淳賢
  • Organizer: 第5回GPCR研究会シンポジウム
  • Place of Presentation: 東京、日本科学未来館
• [Presentation] リゾホスファチジン酸の病態・生理機能 (2007)
  • Author(s): 青木淳賢
  • Organizer: BMB2007
  • Place of Presentation: 横浜, パシフィコ横浜
• [Presentation] リゾホスファチジルセリンによるマスト細胞活性化機構の解析 (2007)
  • Author(s): 巻出久美子、新井洋由、青木淳賢
  • Organizer: BMB2007
  • Place of Presentation: 横浜, パシフィコ横浜
• [Presentation] 生理活性脂質研究の新しい流れ (2007)
  • Author(s): 青木淳賢
  • Organizer: 生体膜と薬物の相互作用シンポジウム
  • Place of Presentation: 仙台
• [Presentation] Autotaxin stabilizes blood vessels and is required for embryonic vasculature by producing lysophosphatidic acid (2007)
  • Author(s): Junken Aoki
  • Organizer: The 3rd International conference on phospholipases A2 and lipid mediators
  • Place of Presentation: Sorrento, Italy