HOSODA Ryuushuke

写真a

Affiliation

School of Medicine, Department of Pharmacology

Job title

Assistant Professor
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Degree 【 display / non-display 】

  • 札幌医科大学   医学博士

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Professional Memberships 【 display / non-display 】

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    THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

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    THE JAPANESE PHARMACOLOGICAL SOCIETY

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Research Areas 【 display / non-display 】

  • Life sciences   Pharmacology  

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Affiliation 【 display / non-display 】

  • Sapporo Medical University   医学部 薬理学講座   助教  

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Research Interests 【 display / non-display 】

  • Autophagy

  • Mitophagy

  • Mitochondria

  • Aging

  • Skeletal muscle

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Papers 【 display / non-display 】

  • Transcriptional dysregulation of autophagy in the muscle of a mouse model of Duchenne muscular dystrophy

    Ryuta Nakashima, Ryusuke Hosoda, Yuki Tatekoshi, Naotoshi Iwahara, Yukika Saga, Atsushi Kuno

    Scientific Reports   14, ( 1365 )  2024.01  [Refereed]

    DOI

  • Resveratrol, a SIRT1 activator, attenuates aging-associated alterations in skeletal muscle and heart in mice.

    Ryusuke Hosoda, Ryuta Nakashima, Masaki Yano, Naotoshi Iwahara, Seidai Asakura, Iyori Nojima, Yukika Saga, Risa Kunimoto, Yoshiyuki Horio, Atsushi Kuno

    Journal of Pharmacological Sciences ( Elsevier BV )   2023.04  [Refereed]

    Authorship：   Lead author

    DOI

  • No sex differences in the acute effects of caffeine on mental calculation and pulse rate in healthy college students.

    Nobuyuki Kurokawa, Rumi Niwa, Kouhei Tada, Ryusuke Hosoda, Naotoshi Iwahara, Yoshiyuki Horio, Atsushi Kuno

    Clinical Nutrition Open Science ( Elsevier BV )   2023.02  [Refereed]

    DOI

  • Activation of SIRT1 promotes membrane resealing via cortactin

    Naotoshi Iwahara, Kuya Azekami, Ryusuke Hosoda, Iyori Nojima, Shin Hisahara, Atsushi Kuno

    Scientific Reports ( Springer Science and Business Media LLC )  12 ( 1 ) 15328 - 15328  2022.09  [Refereed]  [International journal]

    　View Summary

    Abstract Muscular dystrophies are inherited myopathic disorders characterized by progressive muscle weakness. Recently, several gene therapies have been developed; however, the treatment options are still limited. Resveratrol, an activator of SIRT1, ameliorates muscular function in muscular dystrophy patients and dystrophin-deficient mdx mice, although its mechanism is still not fully elucidated. Here, we investigated the effects of resveratrol on membrane resealing. We found that resveratrol promoted membrane repair in C2C12 cells via the activation of SIRT1. To elucidate the mechanism by which resveratrol promotes membrane resealing, we focused on the reorganization of the cytoskeleton, which occurs in the early phase of membrane repair. Treatment with resveratrol promoted actin accumulation at the injured site. We also examined the role of cortactin in membrane resealing. Cortactin accumulated at the injury site, and cortactin knockdown suppressed membrane resealing and reorganization of the cytoskeleton. Additionally, SIRT1 deacetylated cortactin and promoted the interaction between cortactin and F-actin, thus possibly enhancing the accumulation of cortactin at the injury site. Finally, we performed a membrane repair assay using single fiber myotubes from control and resveratrol-fed mice, where the oral treatment with resveratrol promoted membrane repair ex vivo. These findings suggest that resveratrol promotes membrane repair via the SIRT1/cortactin axis.

    DOI PubMed

  • Downregulation of IGFBP5 contributes to replicative senescence via ERK2 activation in mouse embryonic fibroblasts

    Iyori Nojima, Ryusuke Hosoda, Yuki Toda, Yoshiki Saito, Naohiro Ueda, Kouhei Horimoto, Naotoshi Iwahara, Yoshiyuki Horio, Atsushi Kuno

    Aging ( Impact Journals, LLC )  14 ( 7 ) 2966 - 2988  2022.04  [Refereed]  [International journal]

    　View Summary

    Insulin-like growth factor (IGF)-binding proteins (IGFBPs) are secretory proteins that regulate IGF signaling. In this study, we investigated the role of IGFBP5 in replicative senescence in embryonic mouse fibroblasts (MEFs). During passages according to the 3T3 method, MEFs underwent senescence after the 5th passage (P5) based on cell growth arrest, an increase in the number of cells positive for senescence-associated β-galactosidase (SA-β-GAL) staining, and upregulation of p16 and p19. In P8 MEFs, IGFBP5 mRNA level was markedly reduced compared with that in P2 MEFs. Downregulation of IGFBP5 via siRNA in P2 MEFs increased the number of SA-β-GAL-positive cells, upregulated p16 and p19, and inhibited cell growth. Incubation of MEFs with IGFBP5 during serial passage increased the cumulative population doubling and decreased SA-β-GAL positivity compared with those in vehicle-treated cells. IGFBP5 knockdown in P2 MEFs increased phosphorylation levels of ERK1 and ERK2. Silencing of ERK2, but not that of ERK1, blocked the increase in the number of SA-β-GAL-positive cells in IGFBP5-knockdown cells. The reduction in the cell number and upregulation of p16 and p21 in IGFBP5-knockdown cells were attenuated by ERK2 knockdown. Our results suggest that downregulation of IGFBP5 during serial passage contributes to replicative senescence via ERK2 in MEFs.

    DOI PubMed

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Misc 【 display / non-display 】

  • Deletion of SIRT1 in the skeletal muscle decreases type IIa oxidative muscle fiber in mice.

    Ryusuke Hosoda, Atsushi Kuno, Seidai Asakura, Yoshiyuki Horio

    The FASEB Journal ( Wiley )  34 ( S1 ) 1 - 1  2020.04

    Authorship：   Lead author

    Research paper, summary (international conference)  

    DOI

  • Sirt1 Activation Restores Mitophagy-Mediated Clearance of Damaged Mitochondria and Ameliorates Dystrophic Cardiomyopathy in Mice

    Kuno, A, Hosoda, R, Horio, Y

    CIRCULATION   138  2018.11

    Research paper, summary (international conference)  

  • SIRT1は老化関連タンパクPrl2C3を負に制御する(SIRT1 negatively regulates the expression of Prl2C3, a senescence-associated protein)

    堀本 浩平, 國本 梨沙, 橋本 梨沙, 上田 直弘, 細田 隆介, 久野 篤史, 山下 利春, 堀尾 嘉幸

    札幌医学雑誌 ( 札幌医科大学 )  86 ( 1-6 ) 63 - 71  2017.12  [Refereed]

    　View Summary

    SIRT1は酵母の長寿遺伝子Sir2の哺乳類における相同体である。SIRT1はNAD+依存性に転写因子、共同因子、ヒストンを脱アセチル化し、細胞生存、抗酸化機能、DNA修復作用を促進する。SIRT1が長寿に関連することを示す研究報告もあるが、SIRT1の老化予防機能に関しては解明されていない。我々はマウス胚性線維芽細胞(MEF)において、SIRT1の発現が細胞老化によって減少し、SIRT1がプロラクチン類似作用を持つタンパクであるPrl2c3の発現を相反的に制御していることを発見した。精製したPrl2C3タンパクは若いMEFの増殖を抑制し、老化を示すβ-ガラクトシダーゼ陽性のMEFを増加させ、細胞を大型で平坦な形態に変化させた。ヒトの皮膚組織の免疫染色において、Prl2C3は主に表皮内の基底細胞に発現していた。これらの結果は、SIRT1が老関連タンパクであるPrl2C3を負に制御することを示している。(著者抄録)

  • Development of a new remedy for muscular dystrophies

    久野 篤史, 細田 隆介, 堀尾 嘉幸

    Medical Science Digest ( (株)ニュー・サイエンス社 )  42 ( 13 ) 642 - 646  2016.12

    Article, review, commentary, editorial, etc. (other)  

    　View Summary

    SIRT1は酵母で過剰発現させると寿命を延ばす働きをするSir2ホモログで、タンパク質を脱アセチル化する酵素である。SIRT1の活性化を行うレスベラトロールの投与が筋ジストロフィーmdxマウスの骨格筋酸化ストレス量を減少させ筋量の減少を抑制し、さらに線維化を抑制した。また、mdxマウスの心筋においてもその肥大を抑制し、心筋機能を保ち、心筋線維化も抑制することを見出した。本稿ではSIRT1の機能と筋での働きを中心に取り上げる。より詳しい内容については総説を参照されたい。(著者抄録)

  • Impaired Autophagy Induced by Activated mTORC1 Underlies Development of Dystrophic Cardiomyopathy.

    Atsushi Kuno, Ryusuke Hosoda, Rio Sebori

    CIRCULATION ( LIPPINCOTT WILLIAMS & WILKINS )  134  2016.11

    Research paper, summary (international conference)  

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Industrial Property Rights 【 display / non-display 】

  • Type17コラーゲンの産生促進剤

    特許JP6364143B2

    濱田 博喜, 細田 隆介, 小野 翼

    Patent

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Awards 【 display / non-display 】

  • 優秀ポスター賞

    2022.11   第96回日本薬理学会年会   骨格筋におけるSIRT1の活性化はオートファジー活性を維持して加齢によるサルコペニアを改善する

    Winner： 細田 隆介、久野 篤史、中島 龍汰、岩原 直敏、野島 伊世里、堀尾 嘉幸

  • 若手研究者優秀発表賞

    2022.09   第73回日本薬理学会北部会   骨格筋におけるSIRT1の活性化はオートファジー活性を維持して加齢によるサルコペニアを改善する

    Winner： 細田隆介、久野篤史、中島龍太、岩原直敏、野島伊世里、堀尾嘉幸

  • 奨励賞

    2010.09   第61回日本薬理学会北部会   レスベラトロール配糖体の酸化ストレス抑制作用

    Winner： 細田隆介, 堀佑輔, 久野篤史, 濱田博喜, 堀尾嘉幸

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Research Projects 【 display / non-display 】

  • The elucidation of the sarcopenia pathogenic mechanism by protein acetylation modification and its therapeutic applications.

    Project Year :

    2023.04
    -
    2025.03
     

    Authorship： Principal investigator

  • Elucidation of the mechanism of sarcopenia pathogenesis and development of targeted therapies for protein acetylation modification.

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2022.04
    -
    2025.03
     

    細田 隆介

  • レスベラトロールはオートファジーを促進して老化に伴う筋委縮と筋機能低下を改善する

    海外学会等出席研究 交流助成

    Project Year :

    2021.06
    -
    2022.04
     

  • マイトファジー活性をターゲットとした筋ジストロフィーの新規治療法開発

    研究助成

    Project Year :

    2019.09
    -
    2020.03
     

    Authorship： Principal investigator

  • Development of a novel therapeutics for muscular dystrophy by targeting mitophagy.

    Grant-in-Aid for Scientific Research (C)

    Project Year :

    2019.04
    -
    2022.03
     

    Hosoda Ryusuke

    　View Summary

    This study was conducted to elucidate the relationship between the pathogenesis of Duchenne muscular dystrophy (DMD) and impaired mitochondria. mitochondrial DNA from skeletal muscle of DMD model mice was analyzed by next-generation sequencing, but deletion sites could not be identified. On the other hand, the nuclear localization of TFEB, an autophagy-related factor, was significantly reduced in the skeletal muscle of DMD model mice. In the future, we will clarify whether SIRT1 activation shifts the localization of TFEB to the nucleus in DMD. We will then elucidate the mitophagy-promoting mechanism via SIRT1 activation to develop a mitophagy-targeted therapy for muscular dystrophy.

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Presentations 【 display / non-display 】

  • 加齢によるサルコペニアの骨格筋で増加するアセチル化蛋白の網羅的解析

    細田隆介

    第74回日本薬理学会北部会 

    Presentation date： 2023.09

    Event date：
    2023.09
    　
    　

  • Activation of SIRT1 by treatment with resveratrol preserves autophagy and attenuates aging-related sarcopenia in mice.

    Ryusuke Hosoda, Atsushi Kuno, Ryuta Nakashima, Naotoshi Iwahara, Iyori Nojima, Yoshiyuki Horio

    19th World Congress of Basic & Clinical Pharmacology 

    Presentation date： 2023.07

    Event date：
    2023.07
    　
    　

  • The activation of SIRT1 in skeletal muscle preserves autophagic activity and improves age-related sarcopenia（

    Hosoda Ryusuke  [Invited]

    Japan basic and clinical Pharmacology week 2022 

    Presentation date： 2022.12

    Event date：
    2022.11
    -
    2022.12

  • 骨格筋におけるSIRT1の活性化はオートファジー活性を維持して加齢に伴うサルコペニアを改善する

    細田 隆介

    第96回日本薬理学会年会 

    Presentation date： 2022.12

    Event date：
    2022.11
    -
    2022.12

  • 骨格筋におけるSIRT1の活性化はオートファジー活性を維持して加齢によるサルコペニアを改善する

    細田隆介

    第73回日本薬理学会北部会 

    Presentation date： 2022.09

    Event date：
    2022.09
    　
    　

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Teaching Experience 【 display / non-display 】

  • 医学部第一学年副学生担当教員  

    2023.04
    -
    Now
     

  • 薬理学実習（平滑筋と薬物）  

    2021.04
    -
    Now
     

  • 健康行動科学  

    2020.04
    -
    Now
     

  • 臨床検査・薬理学（神経系の薬理学）  

    2020.04
    -
    Now
     

  • 薬理学実習（中枢神経）  

    2019.04
    -
    2020.03
     

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