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Study on the effects of amino acid availability on life span and the underlying molecular mechanisms

Research Project

Project/Area Number 18K19429
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 48:Biomedical structure and function and related fields
Research InstitutionOsaka University

Principal Investigator

Kanai Yoshikatsu  大阪大学, 医学系研究科, 教授 (60204533)

Co-Investigator(Kenkyū-buntansha) 大垣 隆一  大阪大学, 医学系研究科, 助教 (20467525)
奥田 傑  大阪大学, 医学系研究科, 助教 (50511846)
岡西 広樹  大阪大学, 医学系研究科, 助教 (70792589)
Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Keywordsアミノ酸 / トランスポーター / 寿命
Outline of Final Research Achievements

Prolongation of life span by dietary restrictions has been reported in many species. Its fundamental mechanisms behind have been supposed to be in common among species. This research used C. elegans as a model animal and demonstrated that it is possible to restrict whole body amino acid availability by double knockout of an intestinal amino acid transporter with broad substrate selectivity and an intestinal oligopeptide transporter. Furthermore, this research showed that, in this animal model, the restriction of whole-body amino acid availability results in the prolongation of life span.

Academic Significance and Societal Importance of the Research Achievements

食餌制限による寿命の延長効果についてのこれまでの解析では、食餌中から特定の成分のみを厳密に選択的に除くことは困難であり、食餌制限がもたらす寿命への影響を摂取カロリーの減少の影響として一括りに捉えることが多かった。本研究は、線虫を用い、腸管の複数のトランスポーターのノックアウトにより、個体のアミノ酸アベイラビリティを大幅に低下させるモデル系を確立し、アミノ酸栄養の制限による個体寿命の延長を実証したものである。その分子機構の解明は、寿命研究に新たな方向性を提示するものと期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (36 results)

All 2020 2019 2018

All Journal Article (14 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 10 results,  Open Access: 5 results) Presentation (22 results) (of which Int'l Joint Research: 5 results,  Invited: 8 results)

  • [Journal Article] Expression of L-type amino acid transporter 1 as a molecular target for prognostic and therapeutic indicators in bladder carcinoma.2020

    • Author(s)
      Maimaiti M, Sakamoto S, Yamada Y, Sugiura M, Rii J, Takeuchi N, Imamura Y, Furihata T, Ando K, Higuchi K, Xu M, Sazuka T, Nakamura K, Kaneda A, Kanai Y, Kyprianou N, Ikehara Y, Anzai N, Ichikawa T.
    • Journal Title

      Scientific Reports

      Volume: 10 Issue: 1 Pages: 1292-1292

    • DOI

      10.1038/s41598-020-58136-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Targeted alpha therapy using astatine (211At)-labeled phenylalanine: A preclinical study in glioma bearing mice2020

    • Author(s)
      Watabe Tadashi、Kaneda-Nakashima Kazuko、Shirakami Yoshifumi、Liu Yuwei、Ooe Kazuhiro、Teramoto Takahiro、Toyoshima Atsushi、Shimosegawa Eku、Nakano Takashi、Kanai Yoshikatsu、Shinohara Atsushi、Hatazawa Jun
    • Journal Title

      Oncotarget

      Volume: -

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Transporters2019

    • Author(s)
      Alexander SPH, Kelly E, Mathie A, Peters JA, Veale EL, Armstrong JF, Faccenda E, Harding SD, Pawson AJ, Sharman JL, Southan C, Davies JA; CGTP Collaborators.
    • Journal Title

      British Journal of Pharmacology

      Volume: 176 Issue: S1

    • DOI

      10.1111/bph.14753

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] LAT1‐specific inhibitor is effective against T cell‐mediated allergic skin inflammation2019

    • Author(s)
      Hayashi Keitaro、Kaminuma Osamu、Nishimura Tomoe、Saeki Mayumi、Matsuoka Kunie、Hiroi Takachika、Jutabha Promsuk、Iwata Yohei、Sugiura Kazumitsu、Owada Takayoshi、Kurasawa Kazuhiro、Okayasu Isao、Ouchi Motoshi、Fujita Tomoe、Kanai Yoshikatsu、Endou Hitoshi、Anzai Naohiko
    • Journal Title

      Allergy

      Volume: 75 Issue: 2 Pages: 463-467

    • DOI

      10.1111/all.14019

    • NAID

      40022246112

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] CYP450s-Activity Relations of Celastrol to Interact with Triptolide Reveal the Reasons of Hepatotoxicity of Tripterygium wilfordii2019

    • Author(s)
      Jin Chunhuan、Wu Zijun、Wang Lili、Kanai Yoshikatsu、He Xin
    • Journal Title

      Molecules

      Volume: 24 Issue: 11 Pages: 2162-2162

    • DOI

      10.3390/molecules24112162

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Cryo-EM structure of the human L-type amino acid transporter 1 in complex with glycoprotein CD98hc2019

    • Author(s)
      Lee Yongchan、Wiriyasermkul Pattama、Jin Chunhuan、Quan Lili、Ohgaki Ryuichi、Okuda Suguru、Kusakizako Tsukasa、Nishizawa Tomohiro、Oda Kazumasa、Ishitani Ryuichiro、Yokoyama Takeshi、Nakane Takanori、Shirouzu Mikako、Endou Hitoshi、Nagamori Shushi、Kanai Yoshikatsu、Nureki Osamu
    • Journal Title

      Nature Structural & Molecular Biology

      Volume: 26 Issue: 6 Pages: 510-517

    • DOI

      10.1038/s41594-019-0237-7

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Distribution of LAT1-targeting PET tracer was independent of the tumor blood flow in rat xenograft models of C6 glioma and MIA PaCa-22019

    • Author(s)
      Aoki Masanao、Watabe Tadashi、Nagamori Shushi、Naka Sadahiro、Ikeda Hayato、Kongpracha Pornparn、Horitsugi Genki、Kanai Yasukazu、Shimosegawa Eku、Kanai Yoshikatsu、Hatazawa Jun
    • Journal Title

      Annals of Nuclear Medicine

      Volume: 33 Issue: 6 Pages: 394-403

    • DOI

      10.1007/s12149-019-01346-9

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Role of Amino Acid Transporter Expression as a Prognostic Marker in Patients With Surgically Resected Colorectal Cancer2019

    • Author(s)
      OGAWA HIROOMI、KAIRA KYOICHI、MOTEGI YOKO、YOKOBORI TAKEHIKO、TAKADA TAKAHIRO、KATOH RYUJI、OSONE KATSUYA、TAKAHASHI RYO、KATAYAMA CHIKA、OYAMA TETSUNARI、KANAI YOSHIKATSU、YAO TAKASHI、ASAO TAKAYUKI、KUWANO HIROYUKI、SHIRABE KEN
    • Journal Title

      Anticancer Research

      Volume: 39 Issue: 5 Pages: 2535-2543

    • DOI

      10.21873/anticanres.13375

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 次世代シークエンス解析によるシスチン尿症患者新規遺伝子変異の同定と欧米遺伝子型分類の日本人患者妥当性の検討2019

    • Author(s)
      坂本 信一, 納谷 幸男, 茂田 安弘, 藤村 正亮, 阿波 裕輔, 二瓶 直樹, 植田 健, 金井 好克, 三上 和男, 赤倉 功一郎, 正井 基之, 山口 邦雄, 野積 邦義, 伊藤 晴夫, 池原 譲, 安西 尚彦, 市川 智彦
    • Journal Title

      日本尿路結石症学会誌

      Volume: 17 Pages: 105-110

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 【トランスポーターのすべて】トランスポーターを対象とする疾患治療薬の開発 がん細胞のアミノ酸トランスポーターを標的としたがん診断と治療の開発2019

    • Author(s)
      金井 好克
    • Journal Title

      医学のあゆみ

      Volume: 270 Pages: 71-77

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 【最先端プローブによる細胞外微小環境のシグナル計測】PEG結合リン脂質の細胞外表層pHイメージングへの応用 細胞膜アンカー型プローブ骨格としての可能性2019

    • Author(s)
      大垣 隆一, 寺村 裕治, 林 大智, 永森 收志, 高井 まどか, 金井 好克
    • Journal Title

      日本薬理学雑誌

      Volume: 153 Pages: 254-260

    • Related Report
      2019 Annual Research Report
  • [Journal Article] 【食の機能実効分子のサイエンス 食品が生体に与える影響の理解と制御】アミノ酸シグナルの解明からがん治療へ アミノ酸トランスポーター阻害によるがん代謝制御2019

    • Author(s)
      大垣 隆一, 金井 好克
    • Journal Title

      実験医学

      Volume: 37 Pages: 508-513

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Boron delivery for boron neutron capture therapy targeting a cancer-upregulated oligopeptide transporter2019

    • Author(s)
      Miyabe Junji、Ohgaki Ryuichi、Saito Keijiro、Wei Ling、Quan Lili、Jin Chunhuan、Liu Xingming、Okuda Suguru、Nagamori Shushi、Ohki Hiroshi、Yoshino Kazuo、Inohara Hidenori、Kanai Yoshikatsu
    • Journal Title

      Journal of Pharmacological Sciences

      Volume: 139 Issue: 3 Pages: 215-222

    • DOI

      10.1016/j.jphs.2019.01.012

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amino acid transporters revisited: New views in health and disease2018

    • Author(s)
      Kandasamy Palanivel、Gyimesi Gergely、Kanai Yoshikatsu、Hediger Matthias A.
    • Journal Title

      Trends in Biochemical Sciences

      Volume: 43 Issue: 10 Pages: 752-789

    • DOI

      10.1016/j.tibs.2018.05.003

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] アミノ酸トランスポーターを標的としたがんの診断と治療の開発2020

    • Author(s)
      金井 好克
    • Organizer
      日本薬学会北陸支部特別講演会薬物動態学セミナー
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Amino acid transporter LAT1 as a novel molecular target for cancer diagnosis and therapeutics2020

    • Author(s)
      Yoshikatsu Kanai
    • Organizer
      Radiation Oncology Seminar in Mayo Clinic
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] トランスポーター阻害薬:標的同定と基礎薬理から臨床開発へ2020

    • Author(s)
      金井 好克
    • Organizer
      第93回日本薬理学会年会 日本臨床薬理学会共催シンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Critical moieties of aromatic amino acid probes causing renal accumulation in tumor imaging2020

    • Author(s)
      Chunhuan Jin, Ling Wei, Ryuichi Ohgaki, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
    • Organizer
      第93回 日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Suppression of LAT1 in endothelial cells of tumor tissues exhibits an anti-angiogenesis effect2020

    • Author(s)
      Lili Quan, Ryuichi Ohgaki, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
    • Organizer
      第93回 日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Time-course analysis of the changes in intracellular amino acid concentrations and amino acid-related signaling pathways in cancer cells induced by the inhibition of cancer-type amino acid transporter LAT12020

    • Author(s)
      西窪 航, 大垣 隆一, 岡西 広樹, 奥田 傑, 金井 好克
    • Organizer
      第93回 日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] SGLT2阻害薬の作用メカニズムと新たな糖尿病治療薬としての期待2019

    • Author(s)
      金井 好克
    • Organizer
      徳島県病院薬剤師会学術講演会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] アミノ酸輸送系を利用したがん特異的化合物送達-LAT1, LAT2によるPETプローブとBNCTホウ素化合物の評価-2019

    • Author(s)
      金井 好克
    • Organizer
      令和元年度京都大学複合原子力科学研究所専門研究会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Renal cystine transporters and epithelial transport disorders2019

    • Author(s)
      Yoshikatsu Kanai
    • Organizer
      11th BioMedical Transporters Conference (BioMedical Transporters 2019)
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] アミノ酸トランスポーターLAT1を標的とした創薬2019

    • Author(s)
      金井 好克
    • Organizer
      薬物動態談話会 第42 年会
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] ヘテロ二量型アミノ酸トランスポーター複合体LAT1-4F2hcは胎盤の合胞体性栄養膜形成に必須の細胞融合因子である2019

    • Author(s)
      大垣 隆一, 大森 崇弘, 原 早織, 中込 咲綾, 金井 正美, 兼田(中島)加珠子, 奥田 傑, 永森 收志, 金井 好克
    • Organizer
      第66回 日本生化学会近畿支部例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Expression of amino acid transporter LAT1 in the endothelial cells of tumor tissues and its contribution to angiogenesis2019

    • Author(s)
      Lili Quan, Ryuichi Ohgaki, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
    • Organizer
      第135回 日本薬理学会近畿部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Identification of miRNA regulating the expression of cancer-type amino acid transporter LAT1: its potential as an antionco-miRNA2019

    • Author(s)
      劉 星明, 大垣 隆一, 岡西 広樹, 奥田 傑, 金井 好克
    • Organizer
      第136回 日本薬理学会近畿部会
    • Related Report
      2019 Annual Research Report
  • [Presentation] PEPT1-targeted boron delivery for boron neutron capture therapy using BPA-containing dipeptide2019

    • Author(s)
      Junji Miyabe, Ryuichi Ohgaki, Keijiro Saito, Ling Wei, Lili Quan, Chunhuan Jin, Xingming Liu, Suguru Okuda, Shushi Nagamori, Hiroshi Ohki, Kazuo Yoshino, Hidenori Inohara, Yoshikatsu Kanai
    • Organizer
      第92回 日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] Comparative phosphoproteomics between non-competitive and competitive inhibitions of L-type amino acid transporter 1 in cancer cells.2019

    • Author(s)
      Kongpracha Pornparn、Wiriyasermkul Pattama、田中 容子、奥田 傑、大垣 隆一、金井 好克、永森 收志
    • Organizer
      第92回 日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] アミノ酸アベイラビリティが細胞内遊離アミノ酸濃度に与える影響2019

    • Author(s)
      西窪 航、大垣 隆一、岡西 広樹、奥田 傑、金井 好克
    • Organizer
      第92回 日本薬理学会年会
    • Related Report
      2018 Research-status Report
  • [Presentation] アミノ酸トランスポーターによる多様な細胞機能制御と創薬標的としての意義2019

    • Author(s)
      大垣隆一
    • Organizer
      第393回 大阪大学臨床栄養研究会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] BPA-dipeptides, novel boron delivery agents for boron neutron capture therapy, are transported by oligopeptide transporter2018

    • Author(s)
      Junji Miyabe, Ryuichi Ohgaki, Keijiro Saito, Ling Wei, Suguru Okuda, Shushi Nagamori, Hiroshi Ohki, Kazuo Yoshino, Hidenori Inohara, Yoshikatsu Kanai
    • Organizer
      18th World congress of basic and clinical pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Phosphoproteome analysis reveals novel cellular responses affect by inhibition of LAT1, a cancer type amino acid transporter.2018

    • Author(s)
      Pornparn Kongpracha, Shushi Nagamori, Pattama Wiriyasermkul, Suguru Okuda, Ryuichi Ohgaki, Yoshikatsu Kanai
    • Organizer
      18th World congress of basic and clinical pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Combination of amino acids necessary and sufficient for the optimal activation of mTORC12018

    • Author(s)
      Ryuichi Ohgaki, Chunhuan Jin, Suguru Okuda, Shushi Nagamori, Yoshikatsu Kanai
    • Organizer
      18th World congress of basic and clinical pharmacology
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] ペプチドトランスポーターを標的としたホウ素中性子捕捉療法に用いる新規ペプチド型ホウ素化合物の検討2018

    • Author(s)
      宮部淳二、大垣隆一、齋藤桂似郎、Wei Ling、奥田傑、永森收志、大木寛、吉野和夫、猪原秀典、金井好克
    • Organizer
      第133回 日本薬理学会近畿部会
    • Related Report
      2018 Research-status Report
  • [Presentation] アミノ酸トランスポーターを介した代謝制御と細胞機能制御2018

    • Author(s)
      大垣隆一、金井好克
    • Organizer
      第72回 日本栄養・食糧学会大会
    • Related Report
      2018 Research-status Report

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Published: 2018-07-25   Modified: 2021-02-19  

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