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Regulation of cellular senescence via starvation-induced reactive sulfur species-signal

Research Project

Project/Area Number 18K11083
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionShowa Pharmaceutical University

Principal Investigator

Watanabe Yasuo  昭和薬科大学, 薬学部, 教授 (10273228)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords血清飢餓 / 活性イオウ / シスタチオニンγ-リアーゼ(CSE) / MAPキナーゼ / 細胞遊走能 / シスタチオニンγ-リアーゼ(CSE) / 活性イオウ分子 / 細胞老化 / 栄養飢餓
Outline of Final Research Achievements

Rate of hydrogen sulfide (H2S) metabolism has recently emerged as the most important factor for calorie restriction-induced longevity in vivo. Here we found increased cystathionine γ-lyase (CSE)-induced cysteine polysulfides, a source of H2S, in a cell upon serum withdrawal in vitro. And cyclic AMP and lipopolysaccharid mimic the increased CSE expression of serum withdrawal. Thus, they might lead to target signaling that mimic the consequences of calorie restriction without the fasting regimens.

Academic Significance and Societal Importance of the Research Achievements

「人生100年時代」を謳う我が国において、健康寿命の延長は極めて重要な課題である。本研究では、カロリー制限による個体長寿を細胞レベルで模倣した。そして、カロリー制限は、イオウ代謝効率を上げて細胞の増殖を遅く(省エネ)していることや、運動や炎症によって、イオウ代謝効率が上がることを示唆した。このことは、正常細胞の健康にとどまらず、一部の腫瘍細胞の増殖を制御できる可能性も含んでいる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (27 results)

All 2020 2019 2018 Other

All Journal Article (7 results) (of which Peer Reviewed: 6 results,  Open Access: 3 results) Presentation (19 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Persulfide Signaling in Stress-Initiated Calmodulin Kinase Response2020

    • Author(s)
      Takata Tsuyoshi、Araki Shoma、Tsuchiya Yukihiro、Watanabe Yasuo
    • Journal Title

      Antioxidants & Redox Signaling

      Volume: 33 Issue: 18 Pages: 1308-1319

    • DOI

      10.1089/ars.2020.8138

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Coordination between Calcium/Calmodulin-Dependent Protein Kinase II and Neuronal Nitric Oxide Synthase in Neurons2020

    • Author(s)
      Araki Shoma、Osuka Koji、Takata Tsuyoshi、Tsuchiya Yukihiro、Watanabe Yasuo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 21 Pages: 7997-7997

    • DOI

      10.3390/ijms21217997

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Oxidative Stress Orchestrates MAPK and Nitric-Oxide Synthase Signal2020

    • Author(s)
      Takata Tsuyoshi、Araki Shoma、Tsuchiya Yukihiro、Watanabe Yasuo
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 21 Issue: 22 Pages: 8750-8750

    • DOI

      10.3390/ijms21228750

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The active-site cysteine residue of Ca2+/calmodulin-dependent protein kinase I is protected from irreversible modification via generation of polysulfidation2019

    • Author(s)
      Takata Tsuyoshi、Tsukuda Ayaka、Tsuchiya Yukihiro、Akaike Takaaki、Watanabe Yasuo
    • Journal Title

      Nitric Oxide

      Volume: 86 Pages: 68-75

    • DOI

      10.1016/j.niox.2019.02.008

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Reactive sulfur species impair Ca2+/calmodulin-dependent protein kinase II via polysulfidation2019

    • Author(s)
      Araki Shoma、Takata Tsuyoshi、Tsuchiya Yukihiro、Watanabe Yasuo
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 508 Issue: 2 Pages: 550-555

    • DOI

      10.1016/j.bbrc.2018.11.134

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Redox regulation of Ca2+/calmodulin-dependent protein kinase IV via oxidation of its active-site cysteine residue2019

    • Author(s)
      Takata Tsuyoshi、Kimura Jun、Ihara Hideshi、Hatano Naoya、Tsuchiya Yukihiro、Watanabe Yasuo
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 130 Pages: 99-106

    • DOI

      10.1016/j.freeradbiomed.2018.10.440

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] 酸化還元状態 Sーグルタチオン化2018

    • Author(s)
      高田剛・土屋幸弘・渡邊泰男
    • Journal Title

      生体の科学

      Volume: 69 Pages: 442-443

    • Related Report
      2018 Research-status Report
  • [Presentation] 血清飢餓によるシスタチオニン γ-リアーゼ発現誘導の意義2020

    • Author(s)
      荒木笙馬、海老澤芳、土屋幸弘、渡邊泰男
    • Organizer
      第20回 日本NO学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] レドックスセンサーとしてのシスタチオニン γ-リアーゼ2020

    • Author(s)
      土屋幸弘、荒木笙馬、渡邊泰男
    • Organizer
      第20回 日本NO学会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Persulfide signaling in LPS-initiated macrophage response2019

    • Author(s)
      渡邊泰男
    • Organizer
      1st International Conference on Persulfide and Sulfur Metabolism in Biology and Medicine Date
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] カルモデュリンキナーゼ群の活性イオウ分子応答性の差異2019

    • Author(s)
      高田剛、土屋幸弘、赤池孝章、渡邊泰男
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Research-status Report
  • [Presentation] 炎症応答における活性イオウ分子によるカルモデュリンキナーゼII活性制御2019

    • Author(s)
      荒木笙馬、高田剛、土屋幸弘、渡邊泰男
    • Organizer
      生体機能と創薬シンポジウム2019
    • Related Report
      2019 Research-status Report
  • [Presentation] カルモデュリンキナーゼIに対する活性イオウ分子の生理的役割2019

    • Author(s)
      岸康二郎、高田剛、土屋幸弘、赤池孝章、渡邊泰男
    • Organizer
      日本生化学会関東支部例会
    • Related Report
      2019 Research-status Report
  • [Presentation] 抗コリン薬として働くノビレチン2019

    • Author(s)
      岩田千宏、土屋幸弘、松下莉子、高田剛、居原秀、渡邊泰男
    • Organizer
      日本生化学会関東支部例会
    • Related Report
      2019 Research-status Report
  • [Presentation] 活性イオウ分子によるマクロファージでのカルモデュリンキナーゼII活性制御2019

    • Author(s)
      久保寺傑、荒木笙馬、高田剛、土屋幸弘、渡邊泰男
    • Organizer
      日本生化学会関東支部例会
    • Related Report
      2019 Research-status Report
  • [Presentation] カルモデュリンキナーゼIのポリスルフィド化とその意義2019

    • Author(s)
      高田剛、佃彩華、土屋幸弘、赤池孝章、渡邊泰男
    • Organizer
      第19回日本NO学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] PC12細胞におけるアセチルコリン信号系とその阻害薬としてのノビレチン2019

    • Author(s)
      土屋幸弘、松下莉子、高田剛、居原秀、渡邊泰男
    • Organizer
      第19回日本NO学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] マクロファージのLPS応答における活性イオウ分子によるカルモデュリンキナーゼII活性制御2019

    • Author(s)
      荒木笙馬、高田剛、土屋幸弘、渡邊泰男
    • Organizer
      第19回日本NO学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] 活性イオウによるリン酸化シグナル制御2018

    • Author(s)
      渡邊泰男
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] カルモデュリンキナーゼIの活性イオウ分子応答性の解明2018

    • Author(s)
      高田剛、土屋幸弘、渡邊泰男
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] 部位特異的S-ポリスルフィド化修飾を介したカルモデュリンキナーゼII活性制御2018

    • Author(s)
      荒木笙馬、高田剛、土屋幸弘、渡邊泰男
    • Organizer
      第91回日本生化学会大会
    • Related Report
      2018 Research-status Report
  • [Presentation] REACTIVE SULFUR SPECIES INHIBIT Ca2+/ CALMODULIN DEPENDENT PROTEIN KINASE II ACTIVITY VIA SITE SPECIFIC S-POLYSULFIDATION2018

    • Author(s)
      Shoma Araki, Tsuyoshi Takata, Yukihiro Tsuchiya, Yasuo Watanabe
    • Organizer
      The 10th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] REGULATION OF CYSTATHIONINE Γ-LYASE BY CYSTEINE HYDROPERSULFIDE2018

    • Author(s)
      Yasuo Watanabe, Shoma Araki, Tsuyoshi Takata, Yukihiro Tsuchiya1, Takaaki Akaike
    • Organizer
      The 10th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] REGULATION OF CALCIUM ION/CALMODULIN-DEPENDENT PROTEIN KINASE I BY S-POLYSULFIDATION2018

    • Author(s)
      Tsuyoshi Takata, Yukihiro Tsuchiya, Yasuo Watanabe
    • Organizer
      The 10th International Conference on the Biology, Chemistry and Therapeutic Applications of Nitric Oxide
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 過酸化水素によるカルモデュリンキナーゼVの活性制御2018

    • Author(s)
      高田剛、居原秀、土屋幸弘、渡邊泰男
    • Organizer
      第71回日本酸化ストレス学会・第18回日本NO学会 合同学術集会
    • Related Report
      2018 Research-status Report
  • [Presentation] NOによるによるシスタチオニンγ-リアーゼ活性制御2018

    • Author(s)
      荒木笙馬、高田剛、土屋幸弘、渡邊泰男
    • Organizer
      第71回日本酸化ストレス学会・第18回日本NO学会 合同学術集会
    • Related Report
      2018 Research-status Report
  • [Remarks] 昭和薬科大学薬理学研究室HP

    • URL

      https://www.shoyaku.ac.jp/research/laboratory/yakuri/teacher/102

    • Related Report
      2018 Research-status Report

URL: 

Published: 2018-04-23   Modified: 2022-01-27  

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