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Enzymological analysis of a trace phosphopilid N-acyl-phosphatidylethanolamine

Research Project

Project/Area Number 16K08589
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
Research InstitutionKagawa University

Principal Investigator

Ueda Natsuo  香川大学, 医学部, 教授 (20193807)

Co-Investigator(Kenkyū-buntansha) 宇山 徹  香川大学, 医学部, 助教 (30457337)
坪井 一人  川崎医科大学, 医学部, 講師 (80346642)
Research Collaborator Hussain Zahir  
Smriti Sultana Binte Mustafiz  
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
KeywordsN-アシルホスファチジルエタノールアミン / リン脂質 / 酵素 / 脂質メディエーター / N-アシルエタノールアミン / N-アシルトランスフェラーゼ / エンドカンナビノイド / PLAATファミリー
Outline of Final Research Achievements

N-Acylphosphatidylethanolamine (N-acyl-PE) is a class of trace phospholipids, which ubiquitously occurs in natural world. N-Acyl-PE serves as a precursor of the lipid mediator N-acylethanolamine and shows membrane-stabilizing effect per se. In this research project, we characterized PLAAT1 (phospholipase A and acyltransferase 1) and cytosolic phospholipase A2-epsilon (cPLA2-epsilon), which are two enzymes functioning as N-acyl-PE-forming N-acyltransferases in humans and mice, and obtained new findings.

Academic Significance and Societal Importance of the Research Achievements

PEからN-アシル-PEを生成する2種類の「N-アシルトランスフェラーゼ」のうち、PLAAT1については新たなアイソフォームをヒトとマウスで見出し、それがヒトでは唯一の転写物であり、核内に局在することを明らかにした。cPLA2εについてはヒトの酵素がマウスの酵素と同様にCa2+要求性の活性を示すことや、同活性がホスファチジルセリン等の酸性リン脂質の存在下で増強されることを見出した。
これらの成果は、これまで不明な点の多かったN-アシルトランスフェラーゼの性状を明らかにした点で、酵素学および脂質生化学の学問の進展に寄与するとともに、医薬品として期待される本酵素の阻害剤の開発に向けて役立つ。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (45 results)

All 2019 2018 2017 2016 Other

All Journal Article (14 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 13 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Int'l Joint Research: 5 results,  Invited: 4 results) Remarks (4 results)

  • [Journal Article] 脂質メディエーター N -アシルエタノールアミンの代謝に関する酵素学的研究2019

    • Author(s)
      上田夏生
    • Journal Title

      ビタミン

      Volume: 93 Pages: 103-114

    • NAID

      130007822424

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The role of intracellular anionic phospholipids in the production of N-acyl-phosphatidylethanolamines by cytosolic phospholipase A2epsilon2018

    • Author(s)
      Binte Mustafiz Smriti Sultana、Uyama Toru、Hussain Zahir、Kawai Katsuhisa、Tsuboi Kazuhito、Araki Nobukazu、Ueda Natsuo
    • Journal Title

      The Journal of Biochemistry

      Volume: 165 Issue: 4 Pages: 343-352

    • DOI

      10.1093/jb/mvy104

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Endocannabinoids and related N-acylethanolamines: biological activities and metabolism2018

    • Author(s)
      Tsuboi Kazuhito、Uyama Toru、Okamoto Yasuo、Ueda Natsuo
    • Journal Title

      Inflammation and Regeneration

      Volume: 38 Issue: 1 Pages: 28-28

    • DOI

      10.1186/s41232-018-0086-5

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphatidylserine-stimulated production of N -acyl-phosphatidylethanolamines by Ca 2+ -dependent N -acyltransferase2018

    • Author(s)
      Hussain Zahir、Uyama Toru、Kawai Katsuhisa、Binte Mustafiz Smriti Sultana、Tsuboi Kazuhito、Araki Nobukazu、Ueda Natsuo
    • Journal Title

      Biochim Biophys Acta-Mol Cell Biol Lipids

      Volume: 1863 Issue: 5 Pages: 493-502

    • DOI

      10.1016/j.bbalip.2018.02.002

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] The Biosynthetic Pathways of N-Acylethanolamines in Mammals2018

    • Author(s)
      Binte Mustafiz Smriti Sultana、Uyama Toru、Hussain Zahir、Tsuboi Kazuhito、Ueda Natsuo
    • Journal Title

      eLS

      Volume: なし Pages: 1-11

    • DOI

      10.1002/9780470015902.a0027711

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] PLAAT(PLA2G16)ファミリー2018

    • Author(s)
      宇山徹、上田夏生
    • Journal Title

      医学のあゆみ

      Volume: 264 Pages: 171-176

    • Related Report
      2017 Research-status Report
  • [Journal Article] Mammalian enzymes responsible for the biosynthesis of N -acylethanolamines2017

    • Author(s)
      Hussain Zahir、Uyama Toru、Tsuboi Kazuhito、Ueda Natsuo
    • Journal Title

      Biochim Biophys Acta-Mol Cell Biol Lipids

      Volume: 1862 Issue: 12 Pages: 1546-1561

    • DOI

      10.1016/j.bbalip.2017.08.006

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] An involvement of phospholipase A/acyltransferase family proteins in peroxisome regulation and plasmalogen metabolism2017

    • Author(s)
      Uyama Toru、Tsuboi Kazuhito、Ueda Natsuo
    • Journal Title

      FEBS Lett

      Volume: 591 Issue: 18 Pages: 2745-2760

    • DOI

      10.1002/1873-3468.12787

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peripheral tissue levels and molecular species compositions of N-acyl-phosphatidylethanolamine and its metabolites in mice lacking N-acyl-phosphatidylethanolamine-specific phospholipase D2017

    • Author(s)
      Inoue Manami、Tsuboi Kazuhito、Okamoto Yoko、Hidaka Mayumi、Uyama Toru、Tsutsumi Toshihiko、Tanaka Tamotsu、Ueda Natsuo、Tokumura Akira
    • Journal Title

      J Biochem

      Volume: 162 Issue: 6 Pages: 449-458

    • DOI

      10.1093/jb/mvx054

    • NAID

      40021421359

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] グリセロホスホジエステラーゼ・ファミリーによるN-アシルエタノールアミンおよびリゾホスファチジン酸の生成2017

    • Author(s)
      坪井一人, 宇山徹,上田夏生
    • Journal Title

      ビタミン

      Volume: 91 Pages: 489-496

    • NAID

      130007472636

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] Comparative analyses of isoforms of the calcium-independent phosphatidylethanolamine N-acyltransferase PLAAT-1 in humans and mice2016

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Rahman, I.A.S., Tsuboi, K., Araki, N., and Ueda, N.
    • Journal Title

      J. Lipid Res.

      Volume: 57 Issue: 11 Pages: 2051-2060

    • DOI

      10.1194/jlr.m071290

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A quantitative study on splice variants of N-acylethanolamine acid amidase in human prostate cancer cells and other cells2016

    • Author(s)
      Sakura, Y., Tsuboi, K., Uyama, T., Zhang, X., Taoka, R., Sugimoto, M., Kakehi, Y., and Ueda, N.
    • Journal Title

      Biochim. Biophys. Acta-Mol. Cell Biol. Lipids

      Volume: 1861 Issue: 12 Pages: 1951-1958

    • DOI

      10.1016/j.bbalip.2016.09.018

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE72016

    • Author(s)
      Rahman, I.A.S., Tsuboi, K., Hussain, Z., Yamashita, R., Okamoto, Y., Uyama, T., Yamazaki, N., Tanaka, T., Tokumura, A., and Ueda, N.
    • Journal Title

      Biochim. Biophys. Acta-Mol. Cell Biol. Lipids

      Volume: 1861 Issue: 12 Pages: 1881-1892

    • DOI

      10.1016/j.bbalip.2016.09.008

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] 明らかになり始めた新規脂質代謝酵素群phospholipase A/acyltransferase (PLAAT) familyの生理機能2016

    • Author(s)
      宇山徹,渡邊政博, 坪井一人, 上田夏生
    • Journal Title

      ビタミン

      Volume: 90 Pages: 379-389

    • NAID

      130006283679

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] Studies with purified cytosolic phospholipase A2εreveal the stimulatory effect of phosphatidylserine on its Ca2+-dependent N-acyltransferase activity2018

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Mustafiz, S.S.B., Tsuboi, K., Araki, N., Ueda, N.
    • Organizer
      第59回日本生化学会中国・四国支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Enhancement of cytosolic phospholipase A2ε-catalyzed formation of N-acyl-phosphatidylethanolamine by phosphatidylserine2018

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Mustafiz, S.S.B., Tsuboi, K., Araki, N., Ueda, N.
    • Organizer
      第60回日本脂質生化学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ホスファチジルセリンによるN-アシルエタノールアミン生合成の制御2018

    • Author(s)
      宇山 徹,Zahir Hussain,川合 克久,Smriti Sultana Binte Mustafiz,坪井 一人,荒木 伸一,上田 夏生
    • Organizer
      日本ビタミン学会第70回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Characterization of cytosolic phospholipase A2ε: phosphatidylserine-stimulated production of N-acyl-phosphatidylethanolamine2018

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Mustafiz, S.S.B., Tsuboi, K., Araki, N., Ueda, N.
    • Organizer
      28th Annual Symposium of the International Cannabinoid Research Society
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Analysis of purified cytosolic phospholipase A2εreveals the stimulatory effect of phosphatidylserine2018

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Mustafiz, S.S.B., Tsuboi, K., Araki, N., Ueda, N
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] N-アシル-ホスファチジルエタノールアミン特異的ホスホリパーゼD欠損マウスの末梢臓器における関連脂質とその代謝経路の解析2018

    • Author(s)
      坪井 一人,井上 愛美,岡本 蓉子,日高 麻由美,宇山 徹,堤 敏彦,田中 保,岡本 安雄,上田 夏生,徳村 彰
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 必須脂肪酸由来の生理活性脂質と関連脂質分子に関する酵素学的研究2018

    • Author(s)
      上田夏生
    • Organizer
      日本ビタミン学会創立70周年記念シンポジウム
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] 脂質メディエーター研究の最前線~マリファナからエンドカンナビノイド、そして脂質生化学へ~2018

    • Author(s)
      上田夏生
    • Organizer
      第10回天然物薬用研究会
    • Related Report
      2018 Annual Research Report
    • Invited
  • [Presentation] cDNA cloning and characterization of long isoform of calcium-independent phospholipase A/acyltransferase-1 (PLAAT-1) that produces N-acyl-phosphatidylethanolamines2017

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Rahman, I.A.S., Tsuboi, K., Araki, N., Ueda, N.
    • Organizer
      第58回日本生化学会中国・四国支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] 前立腺癌細胞株における抗炎症脂質分解酵素N-アシルエタノールアミン水解酸性アミダーゼ(NAAA)のsplice variantの発現解析2017

    • Author(s)
      佐倉雄馬,坪井一人,張霞,筧善行,上田夏生
    • Organizer
      第58回日本生化学会中国・四国支部例会
    • Related Report
      2017 Research-status Report
  • [Presentation] LRATファミリーに属するPLAAT-1の2つのアイソフォームの比較機能解析2017

    • Author(s)
      宇山徹,Zahir Hussain,川合克久,Iffat Ara Sonia Rahman,坪井一人,荒木伸一,上田夏生
    • Organizer
      日本ビタミン学会第69回大会
    • Related Report
      2017 Research-status Report
  • [Presentation] Calcium-independent generation of N-acylphosphatidylethanolamines (NAPEs) by phospholipase A/acyltransferase-1 isoforms in humans and mice2017

    • Author(s)
      Hussain, Z., Uyama, T., Kawai, K., Rahman, I.A.S., Tsuboi, K., Araki, N., Ueda, N.
    • Organizer
      第59回日本脂質生化学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Characterization of isoforms of the calcium-independent N-acyltransferase PLAAT-1 in humans and mice2017

    • Author(s)
      Uyama, T., Hussain, Z., Kawai, K., Rahman, I.A.S., Tsuboi, K., Araki, N., Ueda, N.
    • Organizer
      27th Annual Symposium of the International Cannabinoid Research Society
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 抗炎症脂質パルミトイルエタノールアミドを加水分解するリソソーム酵素NAAAの前立腺癌細胞株におけるスプライスバリアントの発現解析2017

    • Author(s)
      上田夏生,佐倉雄馬,坪井一人,宇山徹,筧善行
    • Organizer
      第38回日本炎症・再生医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Functional expression of human cytosolic phospholipase A2ε as Ca2+-dependent phosphatidylethanolamine N-acyltransferase2017

    • Author(s)
      Hussain, Z., Uyama, T., Tonai, T., Ueda, N.
    • Organizer
      第40回日本分子生物学会年会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report
  • [Presentation] 脂溶性バイオファクターであるN-アシルエタノールアミンの生合成機構2017

    • Author(s)
      宇山徹,坪井一人,上田夏生
    • Organizer
      第40回日本分子生物学会年会・第90回日本生化学会大会
    • Related Report
      2017 Research-status Report
    • Invited
  • [Presentation] バイオファクターであるN-アシルエタノールアミンとリゾホスファチジン酸(LPA)の新規生合成機構2016

    • Author(s)
      坪井 一人,Iffat Ara Sonia Rahman,Zahir Hussain,山下 量平,岡本 蓉子,宇山 徹,田中 保,徳村 彰,上田 夏生
    • Organizer
      第353回脂溶性ビタミン総合研究委員会
    • Place of Presentation
      ホテル伊東ガーデンAGS館(静岡県伊東市)
    • Year and Date
      2016-12-02
    • Related Report
      2016 Research-status Report
  • [Presentation] The phospholipase A/acyltransferase (PLAAT) family proteins: a possible involvement in regulation of peroxisome biogenesis and formation of N-acylated plasmenylethanolamines2016

    • Author(s)
      Ueda, N.
    • Organizer
      The 1st International Plasmalogen Symposium
    • Place of Presentation
      Centennial Hall Kyushu University School of Medicine (Fukuoka, Japan)
    • Year and Date
      2016-11-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Phospholipase A/acyltransferase-3 regulates peroxisome levels by inhibiting Pex19p2016

    • Author(s)
      Uyama, T., Watanabe, M., Kawai, K., Kono, N., Tsuboi, K., Araki, N., Arai, H., Ueda, N.
    • Organizer
      The 1st International Plasmalogen Symposium
    • Place of Presentation
      Centennial Hall Kyushu University School of Medicine (Fukuoka, Japan)
    • Year and Date
      2016-11-07
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] GDE7はリゾホスホリパーゼD型酵素としてN-アシルエタノールアミンとLPAを生成する2016

    • Author(s)
      坪井 一人,Rahman Iffat Ara Sonia,岡本 蓉子,宇山 徹,山崎 尚志,田中 保,徳村 彰,上田 夏生
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター, 東北大学川内北キャンパス(仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] ヒト前立腺癌細胞株及びその他の細胞株におけるN-アシルエタノールアミン水解酸性アミダーゼ(NAAA)のスプライスバリアントの発現解析2016

    • Author(s)
      佐倉 雄馬,坪井 一人,宇山 徹,張 霞,筧 善行,上田 夏生
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター, 東北大学川内北キャンパス(仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Research-status Report
  • [Presentation] A possible involvement of acid ceramidase in the degradation of N-acylethanolamines2016

    • Author(s)
      Tsuboi, K., Tai, T., Okamoto, Y., Yamashita, R., Rahman, I.A.S., Uyama, T., Houchi, H., Tanaka, T., Tokumura, A., Ueda, N.
    • Organizer
      26th Annual Symposium of the International Cannabinoid Research Society
    • Place of Presentation
      Bukovina (Poland)
    • Year and Date
      2016-06-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Presentation] 脂質メディエーターであるN-アシルエタノールアミンとLPAを生成する新規酵素の解析2016

    • Author(s)
      坪井 一人,Iffat Ara Sonia Rahman,岡本 蓉子,宇山 徹,田中 保,徳村 彰,上田 夏生
    • Organizer
      日本ビタミン学会第68回大会
    • Place of Presentation
      富山国際会議場(富山市)
    • Year and Date
      2016-06-17
    • Related Report
      2016 Research-status Report
  • [Presentation] 酸性セラミダーゼによる細胞内N-アシルエタノールアミンの加水分解2016

    • Author(s)
      坪井 一人,田井 達也,岡本 蓉子,山下 量平,Iffat Ara Sonia Rahman,宇山 徹,芳地 一,田中 保,徳村 彰,上田 夏生
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      秋田市にぎわい交流館AU(秋田市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
  • [Presentation] 口腔粘膜上皮細胞に存在する膜結合型リゾホスホリパーゼD2016

    • Author(s)
      松田 璃沙,坪井 一人,岡本 蓉子,山下 量平,Iffat Ara Sonia Rahman,日高 麻由美,山崎 尚志,上田 夏生,田中 保,徳村 彰
    • Organizer
      第58回日本脂質生化学会
    • Place of Presentation
      秋田市にぎわい交流館AU(秋田市)
    • Year and Date
      2016-06-09
    • Related Report
      2016 Research-status Report
  • [Presentation] Glycerophosphodiesterases, GDE4 and GDE7, are novel lysophospholipase D-type enzymes generating N-acylethanolamine and LPA2016

    • Author(s)
      Rahman, I.A.S., Tsuboi, K., Okamoto, Y., Uyama, T., Yamazaki, N., Tanaka, T., Tokumura, A., Ueda, N.
    • Organizer
      第57回日本生化学会中国・四国支部例会
    • Place of Presentation
      高知大学岡豊キャンパス(高知県南国市)
    • Year and Date
      2016-05-27
    • Related Report
      2016 Research-status Report
  • [Presentation] 前立腺癌細胞株におけるN-アシルエタノールアミン水解酸性アミダーゼ(NAAA)splice variantの発現解析2016

    • Author(s)
      佐倉 雄馬,坪井 一人,筧 善行,上田 夏生
    • Organizer
      第104回日本泌尿器科学会総会
    • Place of Presentation
      仙台国際センター他(仙台市)
    • Year and Date
      2016-04-23
    • Related Report
      2016 Research-status Report
  • [Remarks] 香川大学医学部 生体分子医学講座 生化学

    • URL

      http://www.med.kagawa-u.ac.jp/~biochem/index.html

    • Related Report
      2018 Annual Research Report
  • [Remarks] カダイラボ

    • URL

      https://www.kagawa-u.ac.jp/kadailab/22896/

    • Related Report
      2018 Annual Research Report
  • [Remarks] 香川大学医学部生体分子医学講座生化学ホームページ

    • URL

      http://www.med.kagawa-u.ac.jp/~biochem/index.html

    • Related Report
      2017 Research-status Report
  • [Remarks] 香川大学医学部生化学ホームページ

    • URL

      http://www.med.kagawa-u.ac.jp/~biochem/index.html

    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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