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Radiation-induced oxidative modification response of serum albumin and its application to dose/damage prediction

Research Project

Project/Area Number 21H02860
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 52040:Radiological sciences-related
Research InstitutionHirosaki University

Principal Investigator

Kashiwakura Ikuo  弘前大学, 保健学研究科, 特任教授 (00177370)

Co-Investigator(Kenkyū-buntansha) 多田羅 洋太  弘前大学, 医学研究科, 助教 (00443995)
山口 平  弘前大学, 保健学研究科, 助教 (00782822)
伊藤 勝博  弘前大学, 災害・被ばく医療教育センター, 教授 (20322951)
辻口 貴清  弘前大学, 災害・被ばく医療教育センター, 助教 (90737454)
Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2023: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2022: ¥7,150,000 (Direct Cost: ¥5,500,000、Indirect Cost: ¥1,650,000)
Fiscal Year 2021: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Keywords電離放射線 / 生物学的線量評価 / 血清アルブミン / 酸化修飾応答 / 低線量放射線 / バイオマーカー
Outline of Research at the Start

慢性腎不全や糖尿病などの疾病と血清アルブミン(SA)の特異的な酸化修飾の関連性は近年その解明が進んだが,放射線によるSAの具体的な酸化修飾応答の詳細は不明である.申請者らは,インドネシアで新たに見出された高線量自然放射線地域(33~64 mSv/年,平均≒50 mSv/年)住民血液の解析から,線量依存的に血清アルブミンの酸化修飾が認められることを見出した.この発見は,これまで困難とされてきた100 mSv以下の生体応答の新たな生物学的線量評価法の可能性を示唆している.本研究は,放射線によるSAの酸化修飾の特異配列をもとに,新たなハイスループットな生物学的線量評価法の開発を目指す研究である.

Outline of Final Research Achievements

LC/MS/MS analysis of blood from residents of high natural radiation areas (average 70 mSv/year) in Indonesia, mainly due to chronic inhalation exposure to radon and tron, identified several dose-dependent oxidative modification peptides, apart from the 34th cysteine (Cys-34) oxidation of serum albumin. This oxidative modification response of SA was also observed in mice after single irradiation (0.5 to 3 Gy), even in acute external exposure. Subsequently, when the oxidative modification response of SA was analysed before and after CT examinations of multiple trauma patients transported to the Hirosaki University Advanced Emergency Centre, a specific response was observed even at low doses averaging approximately equal to 30 mSv.
Based on these results, the oxidative modification response of SA is expected to be utilised as a biodosimetry marker for acute low-dose exposure.

Academic Significance and Societal Importance of the Research Achievements

血清中に最も高濃度に存在する血清アルブミン(SA)は,活性酸素種により酸化や糖化などの修飾を受け,特にSAの34番目のシステイン(Cys-34)が酸化される.我々は、SAのCys-34酸化とは別の線量依存的な酸化修飾応答を見出したが、放射線は強い酸化ストレスであり,他の酸化ストレス関連疾患(感染症、ガン、糖尿病や老化等)においても特異的な修飾応答が生じている可能性が強く示唆される.今後は、ヒトに特異的なSAの酸化修飾応答ペプチドの迅速かつ高精度な検出方法(デバイス等)開発や様々な疾患との関連性の検討が求められる。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • Research Products

    (16 results)

All 2023 2022 2021

All Journal Article (10 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 10 results,  Open Access: 10 results) Presentation (4 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 1 results)

  • [Journal Article] DAP3-mediated cell cycle regulation and its association with radioresistance in human lung adenocarcinoma cell lines2023

    • Author(s)
      Sato Yoshiaki、Yoshino Hironori、Sato Kota、Kashiwakura Ikuo、Tsuruga Eichi
    • Journal Title

      Journal of Radiation Research

      Volume: - Issue: 3 Pages: 520-529

    • DOI

      10.1093/jrr/rrad016

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Acute Radiation Syndrome-Mitigator Romiplostim and Secreted Extracellular Vesicles Improved Survival in Mice Acutely Exposed to Myelosuppressive Doses of Ionizing Radiation2023

    • Author(s)
      Yamaguchi Masaru、Kashiwakura Ikuo
    • Journal Title

      Biomolecules

      Volume: 13 Issue: 5 Pages: 837-837

    • DOI

      10.3390/biom13050837

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Prediction of hub genes and key pathways associated with the radiation response of human hematopoietic stem/progenitor cells using integrated bioinformatics methods2023

    • Author(s)
      Sato Yoshiaki、Yoshino Hironori、Ishikawa Junya、Monzen Satoru、Yamaguchi Masaru、Kashiwakura Ikuo
    • Journal Title

      Scientific Reports

      Volume: 13 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-023-37981-6

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of biological responses to low-dose radiation in humans2022

    • Author(s)
      Yamaguchi Masaru、Tatara Yota、Nugraha Eka Djatnika、Ramadhani Dwi、Tamakuma Yuki、Sato Yoshiaki、Miura Tomisato、Hosoda Masahiro、Yoshinaga Shinji、Syaifudin Mukh、Kashiwakura Ikuo、Tokonami Shinji
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 184 Pages: 196-207

    • DOI

      10.1016/j.freeradbiomed.2022.04.006

    • Related Report
      2022 Annual Research Report 2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Serum Proteomic and Oxidative Modification Profiling in Mice Exposed to Total Body X-Irradiation2022

    • Author(s)
      Yamaguchi Masaru、Tatara Yota、Nugraha Eka Djatnika、Sato Yoshiaki、Miura Tomisato、Hosoda Masahiro、Syaifudin Mukh、Tokonami Shinji、Kashiwakura Ikuo
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 9 Pages: 1710-1710

    • DOI

      10.3390/antiox11091710

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Oxidative Modification Status of Human Serum Albumin Caused by Chronic Low-Dose Radiation Exposure in Mamuju, Sulawesi, Indonesia2022

    • Author(s)
      Yamaguchi Masaru、Tatara Yota、Nugraha Eka Djatnika、Tamakuma Yuki、Sato Yoshiaki、Miura Tomisato、Hosoda Masahiro、Yoshinaga Shinji、Syaifudin Mukh、Tokonami Shinji、Kashiwakura Ikuo
    • Journal Title

      Antioxidants

      Volume: 11 Issue: 12 Pages: 2384-2384

    • DOI

      10.3390/antiox11122384

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] An Analysis of the Serum Metabolomic Profile for the Radiomitigative Effect of the Thrombopoietin Receptor Agonist Romiplostim in Lethally Whole-Body-Irradiated Mice2022

    • Author(s)
      Sato Yoshiaki、Yamaguchi Masaru、Kashiwakura Ikuo
    • Journal Title

      Metabolites

      Volume: 12 Issue: 2 Pages: 161-161

    • DOI

      10.3390/metabo12020161

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comprehensive exposure assessments from the viewpoint of health in a unique high natural background radiation area, Mamuju, Indonesia2021

    • Author(s)
      Eka Djatnika Nugraha, Masahiro Hosoda, Kusdiana, Untara, June Mellawati, Nurokhim, Yuki Tamakuma, Abarrul Ikram, Mukh Syaifudin, Ryohei Yamada, Naofumi Akata, Michiya Sasaki, Masahide Furukawa, Shinji Yoshinaga, Masaru Yamaguchi, Tomisato Miura, Ikuo Kashiwakura, Shinji Tokonami
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 14578-14578

    • DOI

      10.1038/s41598-021-93983-2

    • NAID

      120007170569

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Support activities in Namie Town, Fukushima undertaken by Hirosaki University2021

    • Author(s)
      Tokonami Shinji、Miura Tomisato、Akata Naofumi、Tazoe Hirofumi、Hosoda Masahiro、Chutima Kranrod、Kudo Hiromi、Ogura Koya、Fujishima Yohei、Tamakuma Yuki、Shimizu Mayumi、Kikuchi Kazutaka、Kashiwakura Ikuo
    • Journal Title

      Annals of the ICRP

      Volume: 50 Issue: 1_suppl Pages: 102-108

    • DOI

      10.1177/01466453211006806

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Simulation study on radiation exposure of emergency medical responders from radioactively contaminated patients2021

    • Author(s)
      Tsujiguchi Takakiyo、Suzuki Yoko、Sakamoto Mizuki、Narumi Kazuki、Ito Katsuhiro、Yasuda Hiroshi、Tokonami Shinji、Kashiwakura Ikuo
    • Journal Title

      Scientific Reports

      Volume: 11 Issue: 1 Pages: 6162-6162

    • DOI

      10.1038/s41598-021-85635-2

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Mechanism of action of the thrombopoietin receptor agonist romiplostim in reducing radiation injury2023

    • Author(s)
      Masaru Yamaguchi and Ikuo Kashiwakura
    • Organizer
      17th INTERNATIONAL CONGRESS FOR RADIATION RESEARCH
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Serum proteomic and oxidative modification profiling in total body X-irradiated mice2022

    • Author(s)
      Ikuo KASHIWAKURA, Masaru YAMAGUCHI, Tota TATARA, Nugraha Djatnika EKA, Yoshiaki SATO, Tomisato MIURA, Masahiro HOSODA, Syaifudin MUKH, Shinji TOKONAMI
    • Organizer
      日本放射線影響学会第65回大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] ヒト血清タンパク質の参加修飾に着目した慢性低線量放射線被ばく線量の検出2022

    • Author(s)
      山口 平,多田羅 洋太,Nugraha Djatnika EKA,Ramaddhani DWI,玉熊 佑紀,佐藤 嘉晃,三浦 富智,細田 正洋,吉永 信治,Syaifudin MUKH,柏倉 幾郎,床次 眞司
    • Organizer
      日本放射線影響学会第65回大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 致死線量放射線ばく露個体に対する国内承認薬ロミプロスチム及び細胞外小胞の放射線緩和効果2021

    • Author(s)
      山口平、柏倉幾郎
    • Organizer
      日本放射線影響学会第64回大会
    • Related Report
      2021 Annual Research Report
  • [Patent(Industrial Property Rights)] 放射線被ばくバイオマーカー及び治療剤2022

    • Inventor(s)
      山口平、柏倉幾郎
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2022-201663
    • Filing Date
      2022
    • Related Report
      2022 Annual Research Report
  • [Patent(Industrial Property Rights)] 放射線被ばくを検出するためのバイオマーカー2021

    • Inventor(s)
      柏倉幾郎、床次眞司、多田羅洋太、E.D. Nugraha他
    • Industrial Property Rights Holder
      弘前大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas

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Published: 2021-04-28   Modified: 2025-01-30  

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