舘越 勇輝

写真a

所属

医学部 薬理学講座

職名

助教

メールアドレス

メールアドレス

ホームページ

https://web.sapmed.ac.jp/pharmacology/index.html

学歴 【 表示 / 非表示

  • 2013年
    -
    2017年

    札幌医科大学大学院   医学研究科博士課程 修了  

  • 2005年
    -
    2011年

    札幌医科大学   医学部医学科 卒業  

学位 【 表示 / 非表示

  • 2017年03月   札幌医科大学大学院医学研究科   博士(医学)

経歴 【 表示 / 非表示

  • 2023年06月
    -
    継続中

    札幌医科大学医学部   薬理学講座   助教

  • 2023年06月
    -
    継続中

    札幌医科大学医学部   循環器・腎臓・代謝内分泌内科学講座   助教

  • 2018年10月
    -
    2023年05月

    米国ノースウエスタン大学医学部   ファインバーグ心臓血管腎臓研究所   博士研究員

  • 2018年04月
    -
    2018年09月

    北海道立江差病院   循環器内科   医長

  • 2017年04月
    -
    2018年03月

    社会医療法人母恋 天使病院   循環器内科   診療医

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所属学協会 【 表示 / 非表示

  • 2024年08月
    -
    継続中

    日本分子生物学会

  • 2023年08月
    -
    継続中

    U-45 国際心臓研究学会

  • 2023年08月
    -
    継続中

    日本薬理学会

  • 2018年02月
    -
    継続中

    American Heart Association

  • 2017年05月
    -
    継続中

    日本心不全学会

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研究分野 【 表示 / 非表示

  • ライフサイエンス   病態医化学   タンパク質糖鎖付加

  • ライフサイエンス   医化学   メタボロミクス解析

  • ライフサイエンス   循環器内科学   心不全

researchmapの所属 【 表示 / 非表示

  • 札幌医科大学医学部   薬理学講座   助教  

 

研究キーワード 【 表示 / 非表示

  • 左室駆出率の保たれた心不全

  • 心不全

  • 糖鎖付加

  • 糖尿病

  • 内皮細胞

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論文 【 表示 / 非表示

  • Human induced pluripotent stem cell-derived cardiomyocytes to study inflammation-induced aberrant calcium transient.

    Yuki Tatekoshi, Chunlei Chen, Jason Solomon Shapiro, Hsiang-Chun Chang, Malorie Blancard, Davi M Lyra-Leite, Paul W Burridge, Matthew Feinstein, Richard D'Aquila, Priscilla Hsue, Hossein Ardehali

    eLife   13  2024年09月  [国際誌]

     概要を見る

    Heart failure with preserved ejection fraction (HFpEF) is commonly found in persons living with HIV (PLWH) even when antiretroviral therapy suppresses HIV viremia. However, studying this condition has been challenging because an appropriate animal model is not available. In this article, we studied calcium transient in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in culture to simulate the cardiomyocyte relaxation defect noted in PLWH and HFpEF and assess whether various drugs have an effect. We show that treatment of hiPSC-CMs with inflammatory cytokines (such as interferon-γ or TNF-α) impairs their Ca2+ uptake into sarcoplasmic reticulum and that SGLT2 inhibitors, clinically proven as effective for HFpEF, reverse this effect. Additionally, treatment with mitochondrial antioxidants (like mito-Tempo) and certain antiretrovirals resulted in the reversal of the effects of these cytokines on calcium transient. Finally, incubation of hiPSC-CMs with serum from HIV patients with and without diastolic dysfunction did not alter their Ca2+-decay time, indicating that the exposure to the serum of these patients is not sufficient to induce the decrease in Ca2+ uptake in vitro. Together, our results indicate that hiPSC-CMs can be used as a model to study molecular mechanisms of inflammation-mediated abnormal cardiomyocyte relaxation and screen for potential new interventions.

    DOI PubMed

  • Mitochondria regulate proliferation in adult cardiac myocytes

    Gregory B. Waypa, Kimberly A. Smith, Paul T. Mungai, Vincent J. Dudley, Kathryn A. Helmin, Benjamin D. Singer, Clara Bien Peek, Joseph Bass, Lauren Nelson, Sanjiv J. Shah, Gaston Ofman, J. Andrew Wasserstrom, William A. Muller, Alexander V. Misharin, G.R. Scott Budinger, Hiam Abdala-Valencia, Navdeep S. Chandel, Danijela Dokic, Elizabeth Bartom, Shuang Zhang, Yuki Tatekoshi, Amir Mahmoodzadeh, Hossein Ardehali, Edward B. Thorp, Paul T. Schumacker

    Journal of Clinical Investigation ( American Society for Clinical Investigation )  134 ( 13 )  2024年05月  [査読有り]

    DOI

  • Downregulation of Mitochondrial Fusion Protein Expression Affords Protection from Canonical Necroptosis in H9c2 Cardiomyoblasts

    Yuki Toda, Sang-Bing Ong, Toshiyuki Yano, Atsushi Kuno, Hidemichi Kouzu, Tatsuya Sato, Wataru Ohwada, Yuki Tatekoshi, Toshifumi Ogawa, Masaki Shimizu, Masaya Tanno, Masato Furuhashi

    International Journal of Molecular Sciences ( MDPI AG )  25 ( 5 ) 2905 - 2905  2024年03月  [査読有り]

     概要を見る

    Necroptosis, a form of necrosis, and alterations in mitochondrial dynamics, a coordinated process of mitochondrial fission and fusion, have been implicated in the pathogenesis of cardiovascular diseases. This study aimed to determine the role of mitochondrial morphology in canonical necroptosis induced by a combination of TNFα and zVAD (TNF/zVAD) in H9c2 cells, rat cardiomyoblasts. Time-course analyses of mitochondrial morphology showed that mitochondria were initially shortened after the addition of TNF/zVAD and then their length was restored, and the proportion of cells with elongated mitochondria at 12 h was larger in TNF/zVAD-treated cells than in non-treated cells (16.3 ± 0.9% vs. 8.0 ± 1.2%). The knockdown of dynamin-related protein 1 (Drp1) and fission 1, fission promoters, and treatment with Mdivi-1, a Drp-1 inhibitor, had no effect on TNF/zVAD-induced necroptosis. In contrast, TNF/zVAD-induced necroptosis was attenuated by the knockdown of mitofusin 1/2 (Mfn1/2) and optic atrophy-1 (Opa1), proteins that are indispensable for mitochondrial fusion, and the attenuation of necroptosis was not canceled by treatment with Mdivi-1. The expression of TGFβ-activated kinase (TAK1), a negative regulator of RIP1 activity, was upregulated and the TNF/zVAD-induced RIP1-Ser166 phosphorylation, an index of RIP1 activity, was mitigated by the knockdown of Mfn1/2 or Opa1. Pharmacological TAK1 inhibition attenuated the protection afforded by Mfn1/2 and Opa1 knockdown. In conclusion, the inhibition of mitochondrial fusion increases TAK1 expression, leading to the attenuation of canonical necroptosis through the suppression of RIP1 activity.

    DOI

  • Role of AMP deaminase in diabetic cardiomyopathy

    Tetsuji Miura, Hidemichi Kouzu, Masaya Tanno, Yuki Tatekoshi, Atsushi Kuno

    Molecular and Cellular Biochemistry ( Springer Science and Business Media LLC )   2024年02月  [査読有り]

    DOI

  • 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 ( 1 ) 1365 - 1365  2024年01月  [査読有り]  [国際誌]

     概要を見る

    It has been reported that autophagic activity is disturbed in the skeletal muscles of dystrophin-deficient mdx mice and patients with Duchenne muscular dystrophy (DMD). Transcriptional regulations of autophagy by FoxO transcription factors (FoxOs) and transcription factor EB (TFEB) play critical roles in adaptation to cellular stress conditions. Here, we investigated whether autophagic activity is dysregulated at the transcription level in dystrophin-deficient muscles. Expression levels of autophagy-related genes were globally decreased in tibialis anterior and soleus muscles of mdx mice compared with those of wild-type mice. DNA microarray data from the NCBI database also showed that genes related to autophagy were globally downregulated in muscles from patients with DMD. These downregulated genes are known as targets of FoxOs and TFEB. Immunostaining showed that nuclear localization of FoxO1 and FoxO3a was decreased in mdx mice. Western blot analyses demonstrated increases in phosphorylation levels of FoxO1 and FoxO3a in mdx mice. Nuclear localization of TFEB was also reduced in mdx mice, which was associated with elevated phosphorylation levels of TFEB. Collectively, the results suggest that autophagy is disturbed in dystrophin-deficient muscles via transcriptional downregulation due to phosphorylation-mediated suppression of FoxOs and TFEB.

    DOI PubMed

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Misc 【 表示 / 非表示

  • Impact of Mitochondrial Dynamics on Necroptosis in Cardiomyocytes(タイトル和訳中)

    戸田 悠貴, 矢野 俊之, 久野 篤史, 丹野 雅也, 神津 英至, 佐藤 達也, 大和田 渉, 舘越 勇輝, 小川 俊史, 清水 将輝, 古橋 眞人

    日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  88回   PJ080 - 3  2024年03月

  • Administration of Nicotinamide Mononucleotide, a Precursor of NAD+, Attenuates Doxorubicin-induced Cardiotoxicity and Renal Tubular Injury in Mice(タイトル和訳中)

    齊藤 圭司, 細田 隆介, 嵯峨 幸夏, 舘越 勇輝, 久野 篤史

    日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  88回   PJ114 - 4  2024年03月

  • DNA damage and nuclear morphological changes in cardiac hypertrophy are mediated by SNRK through actin depolymerization.

    Paulina Stanczyk, Yuki Tatekoshi, Jason S Shapiro, Krithika Nayudu, Yihan Chen, Zachary Zilber, Matthew Schipma, Adam De Jesus, Amir Mahmoodzadeh, Ashley Akrami, Hsiang-Chun Chang, Hossein Ardehali

    bioRxiv : the preprint server for biology    2023年07月   [ 国際誌 ]

    担当区分:   筆頭著者

    機関テクニカルレポート,技術報告書,プレプリント等  

     概要を見る

    BACKGROUND: Proper nuclear organization is critical for cardiomyocyte (CM) function, as global structural remodeling of nuclear morphology and chromatin structure underpins the development and progression of cardiovascular disease. Previous reports have implicated a role for DNA damage in cardiac hypertrophy, however, the mechanism for this process is not well delineated. AMPK family of proteins regulate metabolism and DNA damage response (DDR). Here, we examine whether a member of this family, SNF1-related kinase (SNRK), which plays a role in cardiac metabolism, is also involved in hypertrophic remodeling through changes in DDR and structural properties of the nucleus. METHODS: We subjected cardiac specific (cs)- Snrk -/- mice to trans-aortic banding (TAC) to assess the effect on cardiac function and DDR. In parallel, we modulated SNRK in vitro and assessed its effects on DDR and nuclear parameters. We also used phospho-proteomics to identify novel proteins that are phosphorylated by SNRK. Finally, co-immunoprecipitation (co-IP) was used to verify Destrin (DSTN) as the binding partner of SNRK that modulates its effects on the nucleus and DDR. RESULTS: cs- Snrk -/- mice display worse cardiac function and cardiac hypertrophy in response to TAC, and an increase in DDR marker pH2AX in their hearts. Additionally, in vitro Snrk knockdown results in increased DNA damage and chromatin compaction, along with alterations in nuclear flatness and 3D volume. Phospho-proteomic studies identified a novel SNRK target, DSTN, a member of F-actin depolymerizing factor (ADF) proteins that directly binds to and depolymerize F-actin. SNRK binds to DSTN, and DSTN downregulation reverses excess DNA damage and changes in nuclear parameters, in addition to cellular hypertrophy, with SNRK knockdown. We also demonstrate that SNRK knockdown promotes excessive actin depolymerization, measured by the increased ratio of globular (G-) actin to F-actin. Finally, Jasplakinolide, a pharmacological stabilizer of F-actin, rescues the increased DNA damage and aberrant nuclear morphology in SNRK downregulated cells. CONCLUSIONS: These results indicate that SNRK is a key player in cardiac hypertrophy and DNA damage through its interaction with DSTN. This interaction fine-tunes actin polymerization to reduce DDR and maintain proper CM nuclear shape and morphology. CLINICAL PERSPECTIVE: What is new? Animal hearts subjected to pressure overload display increased SNF1-related kinase (SNRK) protein expression levels and cardiomyocyte specific SNRK deletion leads to aggravated myocardial hypertrophy and heart failure.We have found that downregulation of SNRK impairs DSTN-mediated actin polymerization, leading to maladaptive changes in nuclear morphology, higher DNA damage response (DDR) and increased hypertrophy. What are the clinical implications? Our results suggest that disruption of DDR through genetic loss of SNRK results in an exaggerated pressure overload-induced cardiomyocyte hypertrophy.Targeting DDR, actin polymerization or SNRK/DSTN interaction represent promising therapeutic targets in pressure overload cardiac hypertrophy.

    DOI PubMed

  • Temporal Trends in Mortality Attributable to Heart Failure between 2005 and 2019: Insights from Japanese Vital Statistics(タイトル和訳中)

    田中 仁啓, 舘越 勇輝, 藤本 恒, 夜久 英憲, カーン サディヤ, グリーンランド フィリップ

    日本循環器学会学術集会抄録集 ( (一社)日本循環器学会 )  87回   OJ54 - 5  2023年03月

  • SIRT2 inhibition protects against cardiac hypertrophy and heart failure.

    Xiaoyan Yang, Hsiang-Chun Chang, Yuki Tatekoshi, Maryam Balibegloo, Rongxue Wu, Chunlei Chen, Tatsuya Sato, Jason Shapiro, Hossein Ardehali

    bioRxiv : the preprint server for biology    2023年01月   [ 国際誌 ]

    担当区分:   筆頭著者

    機関テクニカルレポート,技術報告書,プレプリント等  

     概要を見る

    Sirtuins (SIRT) exhibit deacetylation or ADP-ribosyltransferase activity and regulate a wide range of cellular processes in the nucleus, mitochondria and cytoplasm. The role of the only sirtuin that resides in the cytoplasm, SIRT2, in the development of heart failure (HF) and cardiac hypertrophy is not known. In this paper, we show that the hearts of mice with deletion of Sirt2 ( Sirt2 -/- ) display improved cardiac function after ischemia-reperfusion (I/R) and pressure overload (PO), suggesting that SIRT2 exerts maladaptive effects in the heart in response to stress. Similar results were obtained in mice with cardiomyocyte-specific Sirt2 deletion. Mechanistic studies suggest that SIRT2 modulates cellular levels and activity of nuclear factor (erythroid-derived 2)-like 2 (NRF2), which results in reduced expression of antioxidant proteins. Deletion of Nrf2 in the hearts of Sirt2 -/- mice reversed protection after PO. Finally, treatment of mouse hearts with a specific SIRT2 inhibitors reduces cardiac size and attenuates cardiac hypertrophy in response to PO. These data indicate that SIRT2 has detrimental effects in the heart and plays a role in the progression of HF and cardiac hypertrophy, which makes this protein a unique member of the SIRT family. Additionally, our studies provide a novel approach for treatment of cardiac hypertrophy by targeting SIRT2 pharmacologically, providing a novel avenue for the treatment of this disorder.

    DOI PubMed

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産業財産権 【 表示 / 非表示

  • Methods and compositions for treatment of heart failure with preserved ejection fraction

    Yuki Tatekoshi, Hossein Ardehali

    特許権

受賞 【 表示 / 非表示

  • UJA論文賞2024 特別賞

    2024年05月   海外日本人研究者ネットワーク   SNRKが制御するアクチン重合・DNA損傷・心筋肥大  

    受賞者: 舘越 勇輝

  • CPIS賞

    2024年03月   日本循環器学会   ヘキソキナーゼ1の局在変化に伴うO-GlcNAc化蛋白質の増加はHFpEFの発症・進展に寄与する  

  • Best of AHA Specialty Conference: BCVS

    2022年11月   American Heart Association Scientific Session 2022  

  • Best Poster Award

    2016年08月   ESC congress 2016 (Rome)  

  • 第三回新人賞

    2013年10月   日本超音波医学会  

共同研究・競争的資金等の研究課題 【 表示 / 非表示

  • 内皮細胞が制御する耐糖能と5S-GlcNHexの新規糖尿病治療薬としての可能性

    研究期間:

    2024年08月
    -
    2029年03月
     

    舘越 勇輝

    担当区分: 研究代表者

  • 内皮細胞が制御する耐糖能と新規糖尿病治療薬の開発

    研究期間:

    2024年08月
    -
    2025年08月
     

    舘越 勇輝

    担当区分: 研究代表者

  • 血管内皮幹細胞の動態・機能解析に基づくHFpEFの新規治療法の探索

    研究期間:

    2024年07月
    -
    2025年06月
     

    舘越 勇輝

    担当区分: 研究代表者

  • 心臓における血管内皮幹細胞の動態評価とHFpEFへの治療応用

    研究期間:

    2024年07月
    -
    2025年05月
     

    舘越 勇輝

    担当区分: 研究代表者

  • 血管内皮幹細胞の動態・機能解析に基づくHFpEFの新規治療法の探索

    若手研究

    研究期間:

    2024年04月
    -
    2027年03月
     

    舘越 勇輝

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講演・口頭発表等 【 表示 / 非表示

  • SNRKが制御するアクチン重合・DNA損傷・心筋肥大

    舘越 勇輝  [招待有り]

    UJA論文賞2024; オンライン授賞式  

    発表年月: 2024年05月

    開催年月日:
    2024年05月
     
     
  • Protein O-GlcNAcylation in Endothelial Cells Drives the Development of Heart Failure with Preserved Ejection Fraction

    Yuki Tatekoshi

    The 88th Annual Scientific Meeting of the Japanese Circulation Society  

    発表年月: 2024年03月

    開催年月日:
    2024年03月
     
     
  • UJA 留学のすゝめ2023 日本の科学技術を推進するネットワーク構築

     [招待有り]

    第46回日本分子生物学会年会  

    発表年月: 2023年12月

    開催年月日:
    2023年12月
     
     
  • A novel mechanism in the pathogenesis of heart failure with preserved ejection fraction through hexokinase mitochondrial dislocation and substrate shuttling into the O-GlcNAcylation machinery

    Yuki Tatekoshi

    American Heart Association Scientific Sessions 2022  

    発表年月: 2022年11月

    開催年月日:
    2022年11月
     
     
  • Protein O-GlcNAcylation mediated by hexokinase mitochondrial localization underlies the pathogenesis of heart failure with preserved ejection fraction

    Yuki Tatekoshi

    Keystone symposia Heart failure: Mechanism and Therapies  

    発表年月: 2022年10月

    開催年月日:
    2022年09月
    -
    2022年10月

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担当経験のある科目(授業) 【 表示 / 非表示

  • 臨床検査・薬理学  

    札幌医科大学  

    2024年05月
     
     
     

  • PBLチュートリアル  

    札幌医科大学  

    2024年04月
    -
    2024年05月
     

  • 医学概論・医療総論1  

    札幌医科大学  

    2024年01月
     
     
     

  • 生理・薬理実習  

    札幌医科大学  

    2024年01月
     
     
     

  • 研究室 (基礎) 配属  

    札幌医科大学  

    2023年11月
    -
    2023年12月
     

 

委員歴 【 表示 / 非表示

  • 2023年08月
    -
    継続中

      Section leader

  • 2021年07月
    -
    2023年05月

      イリノイ州チーフディレクター

  • 2021年07月
    -
    2023年04月

      幹事

学術貢献活動 【 表示 / 非表示

  • Reviewer for Cardiovascular Diabetology

    査読等

    Cardiovascular Diabetology  

    2024年09月
    -
    継続中
  • Reviewer for Physiological Reports

    査読等

    Physiological Reports  

    2024年06月
    -
    継続中
  • 第88回日本循環器学会学術集会ポスターセッション(日本語) 54 「Heart Failure (Basic) 1」

    学会・研究会等

    日本循環器学会  

    2024年03月
     
     
  • Reviewer for the International Heart Journal

    査読等

    International Heart Journal  

    2023年09月
    -
    継続中
  • UJA論文賞

    審査・学術的助言

    2021年07月
    -
    2023年05月

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