Biochemical and functional analysis of PLAAT family members as lipid-metabolizing enzymes

• Project/Area Number: 15K08278
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kagawa University
• Principal Investigator: Uyama Toru 香川大学, 医学部, 助教 (30457337)
• Co-Investigator(Renkei-kenkyūsha): UEDA Natsuo 香川大学, 医学部, 教授 (20193807) ; TSUBOI Kazuhito 香川大学, 医学部, 助教 (80346642)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: PLAATファミリー / 脂質代謝酵素 / ペルオキシソーム / N-アシル-ホスファチジルエタノールアミン / N-アシルエタノールアミン / cPLA2ε / ホスファチジルセリン / N-アシルホスファチジルエタノールアミン / ホスホリパーゼA1/A2 / リン脂質 / HRASLSファミリー / PLA/ATファミリー

Outline of Final Research Achievements

Phospholipase A/acyltransferase family members consist of five proteins (PLAAT-1-5) and possess lipid-metabolizing activities. In this study, we examined the role of PLAAT-3 in peroxisome metabolism. We also analyzed the N-acyltransferase involved in the biosynthesis of the rare phospholipid species, N-acylphosphatidylethanolamine.

Research Products

• [Journal Article] Phosphatidylserine-stimulated production of N -acyl-phosphatidylethanolamines by Ca 2+ -dependent N -acyltransferase (2018)
  • 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
  • Peer Reviewed
• [Journal Article] The Biosynthetic Pathways of N-acylethanolamines in Mammals (2018)
  • Author(s): Smriti Sultana Binte Mustafiz, Toru Uyama, Zahir Hussain, Kazuhito Tsuboi, and Natsuo Ueda
  • Journal Title: eLS Volume: －
  • Peer Reviewed
• [Journal Article] An involvement of phospholipase A/acyltransferase family proteins in peroxisome regulation and plasmalogen metabolism (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Mammalian enzymes responsible for the biosynthesis of N -acylethanolamines (2017)
  • 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
  • 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 D (2017)
  • 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
  • Peer Reviewed
• [Journal Article] Comparative analyses of isoforms of the calcium-independent phosphatidylethanolamine N-acyltransferase PLAAT-1 in humans and mice (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Calcium-dependent generation of N-acylethanolamines and lysophosphatidic acids by glycerophosphodiesterase GDE7 (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A quantitative study on splice variants of N-acylethanolamine acid amidase in human prostate cancer cells and other cells (2016)
  • 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
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Assay of NAT Activity (2016)
  • Author(s): Toru Uyama and Natsuo Ueda
  • Journal Title: Methods in Molecular Biology Volume: 1412 Pages: 113-122
  • DOI: 10.1007/978-1-4939-3539-0_12
  • ISBN: 9781493935376, 9781493935390
  • Peer Reviewed / Int'l Joint Research
• [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
  • Peer Reviewed
• [Journal Article] Interaction of Phospholipase A/acyltransferase-3 with Pex19p: a Possible Involvement in the Downregulation of Peroxisomes (2015)
  • Author(s): Toru Uyama, Katsuhisa Kawai, Nozomu Kono, Masahiro Watanabe, Kazuhito Tsuboi, Tomohito Inoue, Nobukazu Araki, Hiroyuki Arai, and Natsuo Ueda
  • Journal Title: Journal of Biological Chemistry Volume: 290 Issue: 28 Pages: 17520-17534
  • DOI: 10.1074/jbc.m114.635433
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] 新規脂質代謝酵素群PLAATファミリータンパク質の生理機能解析 (2015)
  • Author(s): 宇山 徹、上田 夏生
  • Journal Title: BIO Clinica Volume: 398 Pages: 909-915
  • Peer Reviewed
• [Journal Article] ホスホリパーゼ A/アシルトランスフェラーゼ-3 を 介したペルオキシソームの制御機構 (2015)
  • Author(s): 宇山 徹
  • Journal Title: 生化学 Volume: 87 Pages: 633-635
  • NAID: 40020650314
  • Peer Reviewed
• [Presentation] Characterizaton of isoforms of the calcium-independent N-acyltransferase PLAAT-1 in humans and mice (2017)
  • Author(s): Toru Uyama, Zahir Hussain, Katsuhisa Kawai, Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Nobukazu Araki and Natsuo Ueda
  • Organizer: 27th Annual Symposium of the International Cannabinoid Research Society
  • Int'l Joint Research
• [Presentation] cDNA Cloning and Characterization of Long Isoform of Calcium-independent Phospholipase A/Acyltransferase-1 (PLAAT-1) that Produces N-Acyl-phosphatidylethanolamines (2017)
  • Author(s): Zahir Hussain, Toru Uyama, Katsuhisa Kawai, Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Nobukazu Araki and Natsuo Ueda
  • Organizer: 第58回日本生化学会中国・四国支部例会
• [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
• [Presentation] Calcium-independent Generation of N-Acylphosphatidylethanolamines (NAPEs) by Phospholipase A/Acyltransferase-1 Isoforms in Humans and Mice (2017)
  • Author(s): Zahir Hussain, Toru Uyama, Katsuhisa Kawai, Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Nobukazu Araki and Natsuo Ueda
  • Organizer: 第59回日本脂質生化学会
• [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、Iffat Ara Sonia Rahman、岡本容子、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
  • Year and Date: 2016-09-25
• [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
  • Year and Date: 2016-09-25
• [Presentation] A possible involvement of acid ceramidase in the degradation of N-acylethanolamines (2016)
  • Author(s): Kazuhito Tsuboi, Tatsuya Tai, Yoko Okamoto, Ryouhei Yamashita, Iffat Ara Sonia Rahman, Toru Uyama, Hitoshi Houchi, Tamotsu Tanaka, Akira Tokumura, and Natsuo Ueda
  • Organizer: 26th Annual Symposium of the International Cannabinoid Research Society
  • Place of Presentation: Poland
  • Year and Date: 2016-06-27
  • 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、岡本容子、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
  • Year and Date: 2016-06-17
• [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、岡本容子、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
  • Year and Date: 2016-06-09
• [Presentation] Glycerophosphodiesterases, GDE4 and GDE7, are novel lysophospholipase D-type enzymes generating N-acylethanolamine and LPA (2016)
  • Author(s): Iffat Ara Sonia Rahman, Kazuhito Tsuboi, Yoko Okamoto, Toru Uyama, Naoshi Yamazaki, Tamotsu Tanaka, Akira Tokumura, and Natsuo Ueda
  • Organizer: 第57回日本生化学会中国・四国支部例会
  • Place of Presentation: 高知
  • Year and Date: 2016-05-27
• [Presentation] PLAAT-3はPex19pを介してペルオキシソーム含量を制御する (2015)
  • Author(s): 宇山 徹、渡邊政博、川合克久、河野 望、坪井一人、荒木伸一、新井洋由、上田夏生
  • Organizer: 第38回日本分子生物学会年会・第88回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2015-12-01
• [Presentation] LRATに相同性を示す酵素PLA/AT-3によるペルオキシソーム形成の制御 (2015)
  • Author(s): 宇山 徹、渡邊政博、川合克久、河野 望、坪井一人、荒木伸一、新井洋由、上田夏生
  • Organizer: 日本ビタミン学会第67回大会
  • Place of Presentation: 奈良
  • Year and Date: 2015-06-05
• [Presentation] PLA/AT-3によるペルオキシソーム形成の制御にはPex19pが関与する (2015)
  • Author(s): 宇山 徹、渡邊政博、川合克久、河野 望、坪井一人、荒木伸一、新井洋由、上田夏生
  • Organizer: 第57回日本脂質生化学会
  • Place of Presentation: 東京
  • Year and Date: 2015-05-28
• [Remarks] 香川大学医学部 生体分子医学講座 生化学
  • URL: http://www.kms.ac.jp/~biochem/index.html
• [Remarks] 香川大学医学部生体分子医学講座生化学
  • URL: http://www.kms.ac.jp/~biochem/index.html