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Mecahistic analysis of a protective response of skin tissue to UV genotoxicity

Research Project

Project/Area Number 15H02815
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionTohoku University

Principal Investigator

IKEHATA Hironobu  東北大学, 医学系研究科, 講師 (90250737)

Co-Investigator(Kenkyū-buntansha) 鈴木 隆史  東北大学, 医学系研究科, 講師 (70508308)
Co-Investigator(Renkei-kenkyūsha) MORITA Masanobu  東北大学, 医学系研究科, 助教 (10519094)
YAMAMOTO Masayuki  東北大学, 医学系研究科, 教授 (50166823)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2017: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥9,750,000 (Direct Cost: ¥7,500,000、Indirect Cost: ¥2,250,000)
Keywords紫外線 / 皮膚 / MIS応答 / アポトーシス / 突然変異 / DNA損傷 / 遺伝子組換えマウス / Nrf2 / 活性酸素 / 環境応答 / 細胞・組織 / Mrf2 / 環境 / 細胞・組織
Outline of Final Research Achievements

We studied the mechanism of the response of mutation induction suppression (MIS), a protective response of skin tissue to UV genotoxicity, using a mechanistic model based on the Keap1-Nrf2 system, which controls antioxidative responses in mammalian cells. We performed an analysis of global gene expression changes in the MIS response and detected the induction of genes related to apoptosis and cell proliferation, which suggests that MIS is based on a tissue turnover mechanism with apoptosis and hyperplasia. The analysis has also suggested that the Keap1-Nrf2 system functions in the tissue recovery process from the skin damage produced after UV exposures. We also estimated the amounts of UV-induced DNA damage necessary for the MIS induction.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • Research Products

    (32 results)

All 2018 2017 2016 2015

All Journal Article (10 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 9 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (21 results) (of which Int'l Joint Research: 3 results,  Invited: 9 results) Book (1 results)

  • [Journal Article] Mechanistic considerations on the wavelength-dependent variations of UVR genotoxicity and mutagenesis in skin: Discrimination of UVA-signature from UV-signature mutation2018

    • Author(s)
      H. Ikehata
    • Journal Title

      Photochemical and Photobiological Sciences

      Volume: -

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Quantitative analysis of UV photolesions suggests that cyclobutane pyrimidine dimers produced in mouse skin by UVB are more mutagenic than those produced by UVC.2018

    • Author(s)
      H. Ikehata, T. Mori, T. Douki, J. Cadet, M. Yamamoto
    • Journal Title

      Photochemical and Photobiological Sciences

      Volume: 17 Pages: 404-413

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Hyperactivation of Nrf2 leads to hypoplasia of bone in vivo.2018

    • Author(s)
      Yoshida E, Suzuki T, Morita M, Taguchi K, Tsuchida K, Motohashi H, Doita M, and Yamamoto M
    • Journal Title

      Genes to Cells

      Volume: - Issue: 5 Pages: 386-392

    • DOI

      10.1111/gtc.12579

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Stress-sensing mechanisms and the physiological roles of the Keap1-Nrf2 system during cellular stress.2017

    • Author(s)
      T. Suzuki, M. Yamamoto
    • Journal Title

      Journal of Biological Chemistry

      Volume: 292 Issue: 41 Pages: 16817-16824

    • DOI

      10.1074/jbc.r117.800169

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hyperactivation of Nrf2 in early tubular development induces nephrogenic diabetes insipidus.2017

    • Author(s)
      Suzuki T, Seki S, Hiramoto K, Naganuma E, Kobayashi EH, Yamaoka A, Baird L, Takahashi N, Sato H, Yamamoto M.
    • Journal Title

      Nat Commun

      Volume: 8 Issue: 1 Pages: 14577-14577

    • DOI

      10.1038/ncomms14577

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Wavelength dependence of UVR-induced mutation spectrum in mouse skin.2016

    • Author(s)
      H. Ikehata
    • Journal Title

      Photomedicine and Photobiology

      Volume: 38 Pages: 1-2

    • Related Report
      2016 Annual Research Report
  • [Journal Article] Absolute Amounts and Status of the Nrf2-Keap1-Cul3 Complex within Cells.2016

    • Author(s)
      Iso T, Suzuki T, Baird L, Yamamoto M.
    • Journal Title

      Mol Cell Biol

      Volume: 36 Issue: 24 Pages: 3100-3112

    • DOI

      10.1128/mcb.00389-16

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Characterizations of Three Major Cysteine Sensors of Keap1 in Stress Response2016

    • Author(s)
      Saito R, Suzuki T, Hiramoto K, Asami S, Naganuma E, Suda H, Iso T, Yamamoto H, Morita M, Baird L, Furusawa Y, Negishi T, Ichinose M, Yamamoto M.
    • Journal Title

      Molecular and Cellular Biology.

      Volume: 36 Issue: 2 Pages: 271-284

    • DOI

      10.1128/mcb.00868-15

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] In vivo spectrum of UVC-induced mutation in mouse skin epidermis may reflect the cytosine deamination propensity of cyclobutane pyrimidine dimers.2015

    • Author(s)
      H. Ikehata, T. Mori and M. Yamamoto
    • Journal Title

      Photochem. Photobiol.

      Volume: 91 Issue: 6 Pages: 1488-1496

    • DOI

      10.1111/php.12525

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Molecular basis of the Keap1-Nrf2 system2015

    • Author(s)
      T. Suzuki, M. Yamamoto
    • Journal Title

      Free Radical Biology and Medicine

      Volume: 88 Pages: 93-100

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Presentation] 紫外線の突然変異スペクトルと皮膚がん特異的突然変異2017

    • Author(s)
      池畑広伸
    • Organizer
      太陽紫外線防御研究委員会第27回シンポジウム
    • Place of Presentation
      大阪大学中之島センター(大阪市)
    • Year and Date
      2017-03-17
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] マウス皮膚に対する広帯域および狭帯域UVBのゲノム毒性の比較2017

    • Author(s)
      池畑広伸, 森俊雄, 山本雅之
    • Organizer
      第39回日本光医学・光生物学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] マウス皮膚における紫外線DNA損傷量と誘発突然変異頻度の定量的関係の解析2017

    • Author(s)
      池畑広伸,森俊雄,山本雅之
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 尿細管発生期における転写因子Nrf2の恒常的活性化は腎性尿崩症を引き起こす2017

    • Author(s)
      鈴木隆史, 関詩織, 長沼絵里子, 高橋信行, 佐藤博, 山本雅之
    • Organizer
      第60回日本腎臓学会学術会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Keap1-Nrf2システムによる酸化ストレス応答機構2017

    • Author(s)
      鈴木隆史, 山本雅之
    • Organizer
      第17回日本蛋白質学会大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Keap1-Nrf2系による酸化ストレス防御機構2017

    • Author(s)
      鈴木隆史, 山本雅之
    • Organizer
      第7回日本分子状水素医学生物学会年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 酸化ストレス応答におけるKeap1の構造・相互作用解析2017

    • Author(s)
      井上仁, 村松亜紀, 鈴木隆史, 磯達朗, 小柴生造, 山本雅之
    • Organizer
      第56回NMR討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 尿細管発生期における転写因子Nrf2の恒常的活性化は腎性尿崩症を引き起こす2017

    • Author(s)
      鈴木隆史, 関詩織, 長沼絵理子, 高橋信行,佐藤博, 山本雅之
    • Organizer
      第40回生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 骨髄球系細胞における転写因子Nrf2活性化がエラスターゼ誘導性肺気腫の形成を阻害する2017

    • Author(s)
      佐藤慶, 鈴木隆史, 長沼絵理子, 杉浦久敏, 一ノ瀬正和, 山本雅之
    • Organizer
      第40回生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 紫外線DNA損傷特異抗体を利用したマウス皮膚における損傷量と誘発突然変異頻度の定量的関係の解析2016

    • Author(s)
      池畑広伸
    • Organizer
      日本放射線影響学会第59回大会,
    • Place of Presentation
      JMSアステールプラザ(広島市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 紫外線ゲノム毒性に対するKEAP1-NRF2系の皮膚防護能2016

    • Author(s)
      池畑広伸、山田亮太郎、山本雅之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Keap1の反応性システイン残基による多様なストレス感知機構2016

    • Author(s)
      鈴木隆史、山本雅之
    • Organizer
      第89回日本生化学会大会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2016-09-25
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Keap1センサーシステイン残基による多様なストレス感知機構2016

    • Author(s)
      鈴木隆史、山本雅之
    • Organizer
      第69回日本酸化ストレス学会学術集会
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2016-08-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] マウス皮膚におけるUVCゲノム毒性の解析 -突然変異スペクトルの波長依存性-2016

    • Author(s)
      池畑広伸
    • Organizer
      第38回日本光医学・光生物学会
    • Place of Presentation
      京都リサーチパーク(京都市)
    • Year and Date
      2016-07-22
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Characterization of three major cysteine sensors of Keap1 in stress response.2016

    • Author(s)
      T. Suzuki, R. Saito, K. Hiramoto, S. Asami, E. Naganuma, H. Suda, T. Iso, H. Yamamoto, M. Morita, L. Baird, Y. Furusawa, T. Negishi, M. Ichinose, M. Yamamoto
    • Organizer
      The 9th International Conference on the Biology, Chemistry, and Therapeutic Applications of Nitric Oxide
    • Place of Presentation
      仙台国際センター(仙台市)
    • Year and Date
      2016-05-20
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 新規変異体創出によるストレスセンサーKeap1のシステイン残基の機能解明2015

    • Author(s)
      斎藤良太、平本圭一郎、浅見颯一郞、鈴木隆史、山本雅之
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] ストレスセンサーKeap1のシステイン変異体ノックインマウスの機能解析2015

    • Author(s)
      浅見颯一郞、斎藤良太、平本圭一郎、鈴木隆史、山本雅之
    • Organizer
      BMB2015
    • Place of Presentation
      神戸ポートアイランド(神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Wavelength dependence of UV photolesion formation and mutagenesis in skin.2015

    • Author(s)
      H. Ikehata
    • Organizer
      16th Congress of the European Society for Photobiology
    • Place of Presentation
      Aveiro, Portugal
    • Year and Date
      2015-08-31
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] マウス皮膚におけるUVCゲノム毒性の解析2015

    • Author(s)
      池畑広伸、森俊雄、山本雅之
    • Organizer
      第37回日本光医学・光生物学会
    • Place of Presentation
      シーガイアコンベンションセンター(宮崎市)
    • Year and Date
      2015-07-17
    • Related Report
      2015 Annual Research Report
  • [Presentation] In vivo analysis of UVC-induced mutation in mouse skin: dose-dependent induction kinetics and mutation spectrum.2015

    • Author(s)
      H. Ikehata, T. Mori, M. Yamamoto
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      京都国際会議場(京都市)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Keap1-Nrf2系による生体防御機構2015

    • Author(s)
      鈴木隆史
    • Organizer
      第64回脳研・高度先進合同セミナー
    • Place of Presentation
      弘前大学(青森県弘前市)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Book] 光と生命の事典2016

    • Author(s)
      池畑広伸,真嶋哲朗、飯野盛利、七田芳則、藤堂剛、秋山(張)秋梅、伊吹裕子、森俊雄、日出間純、錦織千佳子、守田明理、竹内聖二、大平明弘、上出良一、田中淳、船坂陽子、渡辺正勝、森脇真一、菅澤薰、寺西美佳,松永司、安倍学、蟻川謙太郎、安東宏徳、飯郷雅之、池内昌彦、池田憲昭、池田啓、井澤毅、石川大太郎、石川満 他(共著)
    • Total Pages
      422
    • Publisher
      朝倉書店
    • Related Report
      2015 Annual Research Report

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Published: 2015-04-16   Modified: 2019-03-29  

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