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Analysis of novel mechanisms of aging-related diseases focusing on Golgi stress signaling

Research Project

Project/Area Number 19H04030
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionGifu University

Principal Investigator

Oh-hashi Kentaro  岐阜大学, 工学部, 教授 (50332953)

Co-Investigator(Kenkyū-buntansha) 石垣 診祐  滋賀医科大学, 神経難病研究センター, 教授 (40378170)
高島 茂雄  岐阜大学, 糖鎖生命コア研究所, 准教授 (50537610)
天谷 文昌  京都府立医科大学, 医学(系)研究科(研究院), 教授 (60347466)
内尾 こずえ  国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 創薬資源研究支援センター, 主任研究員 (70373397)
Project Period (FY) 2019-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2023: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2022: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsゴルジ体ストレス / CREB3 family / ERAD / ATF6/CREB3 family / FAM143B / 小胞体ストレス / 小胞体関連分解 / CREB3ファミリー / CREB3 / CREB3L2 / FAM134B / ATF6/CREB3ファミリー / TFE3 / ERストレス
Outline of Research at the Start

小胞体で合成された因子が集積し、各種修飾や細胞内の各部位へ輸送を司る『ゴルジ体』の異常と老年性疾患の関連を明らかにする。本研究では、ゴルジ体ストレスセンサーの一つとされるCREB3を中心として検討し、CREB3の活性化制御及び標的因子の解明を行う。それにより、ゴルジストレス応答の包括的理解と加齢性疾患の関わりについて理解を深め、ゴルジ体異常を起因とする疾患に対する新たな予防・治療法の提案を目指す。

Outline of Final Research Achievements

In this study, I focused on CREB3 as one of the Golgi stress signal sensors. In particular, I analyzed the regulation of expression and degradation of CREB3 and CREB3L2 as CREB3 family members, and ATF6, which has a similar structure to CREB3. We also established Neuro2a cells deficient in CREB3 and ATF4, and analyzed putative CREB3-target genes and ER stress inducible genes. Finally, analysis using OSW-1, an anti-tumor compound with a cholesterol skeleton, revealed the existence of an atypical Golgi stress pathway that does not involve CREB3 activation. Our findings are expected to lead to the development of new Golgi-targeted drugs and indicators.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ゴルジ体ストレスセンサーの1つCREB3ファミリーの発現及び分解制御、そして、CREB3のストレス応答への役割について検討を行った。とりわけ、本研究において樹立した各種ERAD不全細胞株、CREB3などのゴルジ体・小胞体ストレス誘導性転写因子欠損細胞株は、今後、ゴルジ体・小胞体ストレスの詳細な解析や薬剤開発に役立つものと考えられる。

Report

(6 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (15 results)

All 2024 2023 2022 2021 2020 2019

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Open Access: 3 results) Presentation (3 results)

  • [Journal Article] Molecular characterization of the ER stress-inducible factor CRELD22024

    • Author(s)
      Shohei Hinaga, Mahmoud Kandeel, Kentaro Oh-hashi
    • Journal Title

      Cell Biochemistry Biophysics

      Volume: -

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elucidation of OSW-1-Induced Stress Responses in Neuro2a Cells2023

    • Author(s)
      Oh-hashi Kentaro、Nakamura Hibiki、Ogawa Hirotaka、Hirata Yoko、Sakurai Kaori
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 6 Pages: 5787-5787

    • DOI

      10.3390/ijms24065787

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Abnormal glomerular basement membrane maturation impairs mesangial cell differentiation during murine postnatal nephrogenesis2023

    • Author(s)
      Uchio-Yamada Kozue、Yasuda Keiko、Oh-Hashi Kentaro、Manabe Noboru
    • Journal Title

      American Journal of Physiology-Renal Physiology

      Volume: 324 Issue: 1 Pages: F124-F134

    • DOI

      10.1152/ajprenal.00192.2022

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular characterization of wild-type and HSAN2B-linked FAM134B2023

    • Author(s)
      Kanamori Akane、Hinaga Shohei、Hirata Yoko、Amaya Fumimasa、Oh-hashi Kentaro
    • Journal Title

      Molecular Biology Reports

      Volume: 50 Issue: 7 Pages: 6005-6017

    • DOI

      10.1007/s11033-023-08517-y

    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the ER-Resident Mannosidase EDEM2 in HEK293 Cells2023

    • Author(s)
      Murase Ryoichi、Kato Genki、Oh-hashi Kentaro
    • Journal Title

      BPB Reports

      Volume: 6 Issue: 6 Pages: 193-199

    • DOI

      10.1248/bpbreports.6.6_193

    • ISSN
      2434-432X
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Expression analysis and functional characterization of thioredoxin domain-containing protein 112022

    • Author(s)
      Murase Ryoichi、Yamamoto Ayumi、Hirata Yoko、Oh-hashi Kentaro
    • Journal Title

      Molecular Biology Reports

      Volume: 49 Issue: 11 Pages: 10541-10556

    • DOI

      10.1007/s11033-022-07932-x

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hypomorphic mutation of PEX3 with peroxisomal mosaicism reveals the oscillating nature of peroxisome biogenesis coupled with differential metabolic activities2022

    • Author(s)
      Takashima Shigeo、Fujita Haruka、Toyoshi Kayoko、Ohba Akiko、Hirata Yoko、Shimozawa Nobuyuki、Oh-hashi Kentaro
    • Journal Title

      Molecular Genetics and Metabolism

      Volume: 137 Issue: 1-2 Pages: 68-80

    • DOI

      10.1016/j.ymgme.2022.07.008

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular characterization of mouse CREB3 regulatory factor in Neuro2a cells.2021

    • Author(s)
      Oh-hashi K, Hasegawa T, Naruse Y, Hirata Y
    • Journal Title

      Mol Biol Rep.

      Volume: 48 Issue: 7 Pages: 5411-5420

    • DOI

      10.1007/s11033-021-06543-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparative Analysis of CREB3 and CREB3L2 Protein Expression in HEK293 Cells.2021

    • Author(s)
      Oh-hashi K, Yamamoto A, Murase R, Hirata Y
    • Journal Title

      Int J Mol Sci

      Volume: 22 Issue: 5 Pages: 2767-2767

    • DOI

      10.3390/ijms22052767

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Characterization of IRE1α in Neuro2a cells by pharmacological and CRISPR/Cas9 approaches.2020

    • Author(s)
      Oh-Hashi K, Kohno H, Kandeel M, Hirata Y
    • Journal Title

      Mol Cell Biochem.

      Volume: 465(1-2) Issue: 1-2 Pages: 53-64

    • DOI

      10.1007/s11010-019-03666-w

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of the ER-bound transcription factor Luman/CREB3 in HEK293 cells.2019

    • Author(s)
      Oh-Hashi K, Takahashi K, Hirata Y.
    • Journal Title

      FEBS Lett.

      Volume: 593(19) Issue: 19 Pages: 2771-2778

    • DOI

      10.1002/1873-3468.13535

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Elucidation of the Molecular Characteristics of Wild-Type and ALS-Linked Mutant SOD1 Using the NanoLuc Complementation Reporter System.2019

    • Author(s)
      Oh-Hashi K, Hirata Y
    • Journal Title

      Appl Biochem Biotechnol.

      Volume: 190(2) Issue: 2 Pages: 674-685

    • DOI

      10.1007/s12010-019-03114-x

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] Neuro2a細胞におけるOSW-1誘導性ストレス応答の解析2023

    • Author(s)
      中村響、櫻井香里、大橋憲太郎
    • Organizer
      日本薬学会東海支部合同学術大会
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Presentation] ERファジー受容体FAM134Bの性状解析2023

    • Author(s)
      金森朱音、大橋憲太郎
    • Organizer
      日本薬学会東海支部合同学術大会
    • Related Report
      2023 Annual Research Report 2022 Annual Research Report
  • [Presentation] HEK293細胞におけるER局在性転写因子Luman/CREB3の調節2019

    • Author(s)
      高橋 貫人 , 平田 洋子 , 大橋 憲太郎
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2025-01-30  

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