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2017 Fiscal Year Annual Research Report

Study of the mechanism of biosynthesis of polysulfurated proteins coupled with translation

Research Project

Project/Area Number 16K15208
Research InstitutionTohoku University

Principal Investigator

赤池 孝章  東北大学, 医学系研究科, 教授 (20231798)

Co-Investigator(Kenkyū-buntansha) 藤井 重元  東北大学, 医学系研究科, 准教授 (00325333)
井田 智章  東北大学, 医学系研究科, 助教 (70570406)
Project Period (FY) 2016-04-01 – 2018-03-31
Keywordsタンパク質ポリサルファ化 / システインポリスルフィド / システイン-tRNA合成酵素 / 活性イオウ分子種
Outline of Annual Research Achievements

本研究では、我々が最近発見したシステイン-tRNA合成酵素(CARS)による生物種横断的なシステインポリスルフィド生合成および翻訳に共役したタンパク質ポリサルファ化の分子メカニズムを解明し、その生理機能を明らかにすることを目的としている。昨年度までの本研究課題において、質量分析(LC-MS/MS)を用いた各種活性イオウ分子種のメタボローム解析およびタンパク質ポリサルファのゲルシフトアッセイとプロテオーム解析により、細菌および哺乳類のCARSのシステインパースルフィド合成活性とタンパク質ポリスルフィド化への関与を明らかにしてきた。本年度は、CARSによるシステインパースルフィド産生およびタンパク質ポリスルフィド化の分子機構について詳細に解析した。その結果、細菌および哺乳類の各種CARSのシステインパースルフィド合成活性の解析により、システインを基質としたシステインパースルフィド産生の酵素反応機構と活性発現に関与するアミノ酸残基を明らかにした。また、無細胞タンパク質合成系と各種アミノ酸変異CARSを用いた解析により、CARSは様々なタンパク質を普遍的にポリサルファ化することが明らかになった。さらに、ミトコンドリアに局在するCARS2を欠損させた細胞の解析により、CARS2によるタンパク質ポリサルファ化がミトコンドリアの伸長・分裂や膜電位形成などの機能制御に深く関わっていることが示された。CARSによる翻訳に共役したシステインパースルフィド産生とタンパク質ポリサルファ化は、ミトコンドリア機能をはじめとした細胞機能制御に重要な役割を果たしていることが示唆された。

  • Research Products

    (38 results)

All 2018 2017 Other

All Int'l Joint Research (4 results) Journal Article (21 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 17 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 7 results,  Invited: 7 results) Book (1 results) Remarks (1 results)

  • [Int'l Joint Research] National Institute of Oncology(Hungary)

    • Country Name
      Hungary
    • Counterpart Institution
      National Institute of Oncology
  • [Int'l Joint Research] University of Southampton(英国)

    • Country Name
      UNITED KINGDOM
    • Counterpart Institution
      University of Southampton
  • [Int'l Joint Research] Sonoma State University/University of Vermont(米国)

    • Country Name
      U.S.A.
    • Counterpart Institution
      Sonoma State University/University of Vermont
  • [Int'l Joint Research] German Cancer Research Center(Germany)

    • Country Name
      Germany
    • Counterpart Institution
      German Cancer Research Center
  • [Journal Article] Involvement of nitric oxide/reactive oxygen species signaling via 8-nitro-cGMP formation in 1-methyl-4-phenylpyridinium ion-induced neurotoxicity in PC12 cells and rat cerebellar granule neurons2018

    • Author(s)
      Masuda K, Tsutsuki H, Kasamatsu S, Ida T, Takata T, Sugiura K, Nishida M, Watanabe Y, Sawa T, Akaike T, Ihara H.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 495 Pages: 2165~2170

    • DOI

      10.1016/j.bbrc.2017.12.088

    • Peer Reviewed
  • [Journal Article] 8-Nitro-cGMP is a promoter of osteoclast differentiation induced by RANKL2018

    • Author(s)
      Kaneko K, Miyamoto Y, Tsukuura R, Sasa K, Akaike T, Fujii S, Yoshimura K, Nagayama K, Hoshino M, Inoue S, Maki K, Baba K, Chikazu D, Kamijo R.
    • Journal Title

      Nitric Oxide

      Volume: 72 Pages: 46~51

    • DOI

      10.1016/j.niox.2017.11.006

    • Peer Reviewed
  • [Journal Article] Important role of endothelial caveolin-1 in the protective role of endothelium-dependent hyperpolarization against nitric oxide-mediated nitrative stress in microcirculation in mice2018

    • Author(s)
      Saito H, Godo S, Sato S, Ito A, Ikumi Y, Tanaka S, Ida T, Fujii S, Akaike T, Shimokawa H.
    • Journal Title

      J Cardiovasc Pharmacol

      Volume: 71 Pages: 113-126

    • DOI

      10.1097/FJC.0000000000000552

    • Peer Reviewed
  • [Journal Article] 8-Nitro-cGMP attenuates the interaction between SNARE complex and complexin through S-guanylation of SNAP-252018

    • Author(s)
      Kishimoto Y, Kunieda K, Kitamura A, Kakihana Y, Akaike T, Ihara H.
    • Journal Title

      ACS Chem Neurosci

      Volume: 9 Pages: 217~223

    • DOI

      10.1021/acschemneuro.7b00363

    • Peer Reviewed
  • [Journal Article] Cysteine perthiosulfenic acid (Cys-SSOH): A novel intermediate in thiol-based redox signaling?2018

    • Author(s)
      Heppner DE, Hristova M, Ida T, Mijuskovic A, Dustin CM, Bogdandi V, Fukuto JM, Dick TP, Nagy P, Li J, Akaike T, van der Vliet A.
    • Journal Title

      Redox Biol

      Volume: 14 Pages: 379~385

    • DOI

      10.1016/j.redox.2017.10.006

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Persulfide synthases function coupled with translation and mediate sulfur respiration2018

    • Author(s)
      Fujii S, Sawa T, Motohashi H, Akaike T.
    • Journal Title

      Br J Pharmacol

      Volume: - Pages: -

    • Peer Reviewed
  • [Journal Article] 概論 レドックス疾患学:レドックス制御の破綻による病態と新たな疾患概念2018

    • Author(s)
      本橋ほづみ、赤池孝章、内田浩二、末松 誠.
    • Journal Title

      実験医学増刊「レドックス疾患学」

      Volume: 36 Pages: 642~648

  • [Journal Article] 硫黄呼吸の発見:ペルスルフィド産生酵素による新しいエネルギー代謝2018

    • Author(s)
      西村 明、赤池孝章.
    • Journal Title

      現代化学

      Volume: 565 Pages: 55~59

  • [Journal Article] Synthesis of L-cysteine derivatives containing stable sulfur isotopes and application of this synthesis to reactive sulfur metabolome2017

    • Author(s)
      Ono K, Jung M, Zhang T, Tsutsuki H, Sezaki H, Ihara H, Wei FY, Tomizawa K, Akaike T, Sawa T.
    • Journal Title

      Free Radic Biol Med

      Volume: 106 Pages: 69~79

    • DOI

      10.1016/j.freeradbiomed.2017.02.023

    • Peer Reviewed
  • [Journal Article] Quantitative determination of polysulfide in albumins, plasma proteins and biological fluid samples using a novel combined assays approach2017

    • Author(s)
      Ikeda M, Ishima Y, Shibata A, Chuang VTG, Sawa T, Ihara H, Watanabe H, Xian M, Ouchi Y, Shimizu T, Ando H, Ukawa M, Ishida T, Akaike T, Otagiri M, Maruyama T.
    • Journal Title

      Anal Chim Acta

      Volume: 969 Pages: 18~25

    • DOI

      10.1016/j.aca.2017.03.027

    • Peer Reviewed
  • [Journal Article] Reactive sulfur species inactivate Ca2+/calmodulin-dependent protein kinase IV via S-polysulfidation of its active-site cysteine residue2017

    • Author(s)
      Takata T, Ihara H, Hatano N, Tsuchiya Y, Akaike T, Watanabe Y.
    • Journal Title

      Biochem J

      Volume: 474 Pages: 2547~2562

    • DOI

      10.1042/BCJ20170092

    • Peer Reviewed
  • [Journal Article] Redox regulation of electrophilic signaling by reactive persulfides in cardiac cells2017

    • Author(s)
      Nishida M, Nishimura A, Matsunaga T, Motohashi H, Kasamatsu S, Akaike T.
    • Journal Title

      Free Radic Biol Med

      Volume: 109 Pages: 132~140

    • DOI

      10.1016/j.freeradbiomed.2017.01.024

    • Peer Reviewed
  • [Journal Article] Disruption of the structural and functional features of surfactant protein A by acrolein in cigarette smoke2017

    • Author(s)
      Takamiya R, Uchida K, Shibata T, Maeno T, Kato M, Yamaguchi Y, Ariki S, Hasegawa Y, Saito A, Miwa S, Takahashi H, Akaike T, Kuroki Y, Takahashi M.
    • Journal Title

      Sci Rep

      Volume: 7 Pages: 8304

    • DOI

      10.1038/s41598-017-08588-5

    • Peer Reviewed / Open Access
  • [Journal Article] 8-Nitro-cGMP promotes bone growth through expansion of growth plate cartilage2017

    • Author(s)
      Hoshino M, Kaneko K, Miyamoto Y, Yoshimura K, Suzuki D, Akaike T, Sawa T, Ida T, Fujii S, Ihara H, Tanaka J, Tsukuura R, Chikazu D, Mishima K, Baba K, Kamijo R.
    • Journal Title

      Free Radic Biol Med

      Volume: 110 Pages: 63~71

    • DOI

      10.1016/j.freeradbiomed.2017.05.022

    • Peer Reviewed
  • [Journal Article] Exposure to electrophiles impairs reactive persulfide-dependent redox signaling in neuronal cells2017

    • Author(s)
      Ihara H, Kasamatsu S, Kitamura A, Nishimura A, Tsutsuki H, Ida T, Ishizaki K, Toyama T, Yoshida E, Abdul Hamid H. Jung M, Matsunaga T, Fujii S, Sawa T, Nishida M, Kumagai Y, Akaike T.
    • Journal Title

      Chem Res Toxicol

      Volume: 30 Pages: 1673~1684

    • DOI

      10.1021/acs.chemrestox.7b00120

    • Peer Reviewed
  • [Journal Article] Chemical biology of hydropersulfides and related species: Possible roles in cellular protection and redox signaling2017

    • Author(s)
      Alvarez L, Bianco CL, Toscano JP, Lin J, Akaike T, Fukuto JM.
    • Journal Title

      Antioxid Redox Signal

      Volume: 27 Pages: 622~633

    • DOI

      10.1089/ars.2017.7081

    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Diversity and microevolution of CRISPR loci in Helicobacter cinaedi2017

    • Author(s)
      Tomida J, Morita Y, Shibayama K, Kikuchi K, Sawa T, Akaike T, Kawamura Y.
    • Journal Title

      PLoS One

      Volume: 12 Pages: e0186241

    • DOI

      10.1371/journal.pone.0186241

    • Peer Reviewed / Open Access
  • [Journal Article] Production of reactive persulfide species in chronic obstructive pulmonary disease2017

    • Author(s)
      Numakura T, Sugiura H, Akaike T, Ida T, Fujii S, Koarai A, Yamada M, Onodera K, Hashimoto Y, Tanaka R, Sato K, Shishikura Y, Hirano T, Yanagisawa S, Fujino N, Okazaki T, Tamada T, Hoshikawa Y, Okada Y, Ichinose M.
    • Journal Title

      Thorax

      Volume: 72 Pages: 1074~1083

    • DOI

      10.1136/thoraxjnl-2016-209359

    • Peer Reviewed
  • [Journal Article] Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics2017

    • Author(s)
      Akaike T, Ida T, Wei FY, Nishida M, Kumagai Y, Alam MM, Ihara H, Sawa T, Matsunaga T, Kasamatsu S, Nishimura A, Morita M, Tomizawa K, Nishimura A, Watanabe S, Inaba K, Shima H, Tanuma N, Jung M, Fujii S, Watanabe Y, Ohmuraya M, Nagy P, Feelisch M, Fukuto JM, Motohashi H.
    • Journal Title

      Nat Commun

      Volume: 8 Pages: 1177

    • DOI

      10.1038/s41467-017-01311-y

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] ニトロ化環状ヌクレオチドと活性イオウ分子によるレドックスシグナル制御と生理機能2017

    • Author(s)
      藤井重元、赤池孝章.
    • Journal Title

      化学療法の領域

      Volume: 33 Pages: 2194~2195

  • [Journal Article] 活性イオウ分子:システインパースルフィドの新規生合成経路の発見とその生理機能2017

    • Author(s)
      西村 明、赤池孝章.
    • Journal Title

      硫酸と工業

      Volume: 70 (11) Pages: 1~9

  • [Presentation] Sulfur respiration in mammals and its implication for tumor biology2018

    • Author(s)
      Takaaki Akaike, Tomoaki Ida, Md. Morshedul Alam, Akira Nishimura, Masanobu Morita, Tetsuro Matsunaga, Hozumi Motohashi.
    • Organizer
      The Cold Spring Harbor Asia Conference on Cancer & Metabolism
    • Int'l Joint Research / Invited
  • [Presentation] システインパースルフィド産生酵素(Cysteine Persulfide Synthase, CPERS)の発見2017

    • Author(s)
      赤池孝章
    • Organizer
      第17回日本NO学会学術集会
    • Invited
  • [Presentation] イオウ呼吸とイオウストレス:ほ乳類における新しいエネルギー代謝とレドックス病態2017

    • Author(s)
      赤池孝章、西村 明、井田智章、松永哲郎、守田匡伸、本橋ほづみ.
    • Organizer
      2017年度生理学研究所研究会「オルガネラダイナミクスの新規制御機構とその病態生理」
    • Invited
  • [Presentation] イオウ呼吸とイオウストレス:新しいエネルギー代謝とレドックス病態の提案2017

    • Author(s)
      赤池孝章、西村 明、井田智章、松永哲郎、守田匡伸、藤井重元、本橋ほづみ.
    • Organizer
      第70回日本酸化ストレス学会学術集会
  • [Presentation] Cysteine polysulfidation governed by cysteinyl-tRNA synthetase (CARSs)2017

    • Author(s)
      Takaaki Akaike
    • Organizer
      Se2017 - 200 Years of Selenium Research (The 11th International Symposium on Selenium in Biology and Medicine and The 5th International Conference on Selenium in the Environment and Human Health)
    • Int'l Joint Research / Invited
  • [Presentation] Cysteinyl-tRNA synthetase (CARS) controls endogenous hydropersulfide production and mediates mitochondrial functions and bioenegetics2017

    • Author(s)
      Takaaki Akaike
    • Organizer
      S-Bio 2017 Plant and Human Sulfur Biology Conference 2017
    • Int'l Joint Research / Invited
  • [Presentation] Discovery of a novel persulfide synthase that mediates mitochondrial sulfur respiration2017

    • Author(s)
      Takaaki Akaike
    • Organizer
      2nd Karolinska-Tohoku Joint Symposium on Medical Sciences
    • Int'l Joint Research / Invited
  • [Presentation] Cysteinyl-tRNA synthetase governs endogenous hydropersulfide production and mediates mitochondrial functions and bioenergetics2017

    • Author(s)
      Takaaki Akaike
    • Organizer
      AARS2017: IUBMB Focused Meeting on Aminoacyl-tRNA Synthetase
    • Int'l Joint Research
  • [Presentation] Moonlighting functions of cysteinyl-tRNA synthetase: Cysteine hydropersulfide production and regulation of mitochondrial biogenesis and bioenergetics2017

    • Author(s)
      Takaaki Akaike, Akira Nishimura, Tomoaki Ida, Tetsuro Matsunaga, Masanobu Morita, Hozumi Motohashi.
    • Organizer
      SfRBM 2017 - 24th Annual Meeting of the Society for Redox Biology and Medicine
    • Int'l Joint Research
  • [Presentation] Cysteinyl-tRNA synthetase (CARS) は活性パースルフィド産生とミトコンドリア機能をコントロールしている2017

    • Author(s)
      赤池孝章
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Invited
  • [Presentation] Cysteine persulfide formation via cysteinyl-tRNA synthetase and its involvement in mitochondrial bioenergetics2017

    • Author(s)
      Takaaki Akaike, Tomoaki Ida, Masanobu Morita, Shigemoto Fujii, Akira Nishimura, Tetsuro Matsunaga, Minkyung Jung, Hozumi Motohashi.
    • Organizer
      8th Joint Meeting of Society for Free Radical Research Australasia and Japan with International Symposium on Coenzyme Q10
    • Int'l Joint Research
  • [Book] Nitric Oxide: Biology and Pathobiology. 3rd ed. (Ignarro LJ, Freeman BA, eds.)2017

    • Author(s)
      Sawa T, Kumagai Y, Akaike T.
    • Total Pages
      403
    • Publisher
      Academic Press
    • ISBN
      978-0-12-804273-1
  • [Remarks] 東北大学大学院医学系研究科 環境医学分野教室ホームページ

    • URL

      http://www.toxicosci.med.tohoku.ac.jp

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Published: 2018-12-17   Modified: 2022-06-16  

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