生理活性リゾリン脂質の機能解明

2007 Fiscal Year Annual Research Report

• Project/Area Number: 19390018
• Research Institution: Tohoku University
• Principal Investigator: 青木 淳賢 Tohoku University, 大学院・薬学研究科, 教授 (20250219)
• Keywords: 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

これまでの研究で3種類の細胞外型ホスホリパーゼA1(PLA1)を同定した。これらPLA1はリゾリン脂質メディエーターの産生を介して作用すると想定されているが、生理機能はほとんど明らかになっていない。本研究では、ホスファチジン酸(PA)を特異的な基質とする膜結合型PA特異的PLA1α(mPA-PLA1α)について遺伝子欠損(KO)マウスを作製し、その生理機能の解明を試みた。mPA-PLA1ア KOマウスは、ヘテロ欠損マウスの交配によりメンデル比に従って誕生し、生後10日目頃から、KOマウスの体毛が縮毛となる形態異常が観察された。毛包組織におけるmPA-PLA1αの発現をin situハイブリダイゼーション法で調べたところ、毛の表皮に分化する毛小皮とこれに接する内根鞘に限局して発現していた。生後10日目のKOマウスと野生型マウスの皮膚について、種々のマーカー遺伝子の発現量をリアルタイムPCRで定量したところ、内根鞘マーカーであるK6irs1/Krt71の発現がKOマウスで有意に低下していた。これらの結果から、mPA-PLA1αは内根鞘において体毛形成に関与することが強く示唆された。

Research Products

• [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] 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