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Possible contribution of oxidative DNA damage 8,5'-purine cyclodeoxynucleosides to progressive neurodegeneration of xeroderma pigmentosum

Research Project

Project/Area Number 24790895
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Neurology
Research InstitutionNara Medical University

Principal Investigator

IWAMOTO Takaaki  奈良県立医科大学, 医学部, 研究助教 (20448773)

Research Collaborator BROOKS P.J.  
NAKANE Hironobu  
HAYASHI Masaharu  
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords酸化的DNA損傷サイクロプリン / 色素性乾皮症 / ヌクレオチド除去修復 / 神経障害 / 国際情報交換, アメリカ
Outline of Final Research Achievements

Xeroderma pigmentosum A group (XP-A) patients develop progressive neurological disease, which has been hypothesized to be associated with the accumulation of a type of oxidative DNA damage called purine 8,5’-cyclo- 2’-deoxynucleosides. Thus, we generated a monoclonal antibody (CdA-1) specific for 8,5’-cyclo-2’-deoxyadenosine (cyclo-dA). An immunoassay using CdA-1 revealed a linear dose response between known amounts of cyclo-dA in oligonucleotides and the antibody binding to them. The quantitative immunoassay revealed that treatment with Fenton-type reagents dose-dependently produces cyclo-dA in DNA. Moreover, immunofluorescent analysis enabled the visualization of cyclo-dA in human cells, which had been transfected with oligonucleotides containing cyclo-dA. Thus, the CdA-1 antibody is a valuable tool for the detection and quantification of cyclo-dA in DNA, and may be useful for characterizing the mechanism(s) underlying the development of XP neurological disease.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • Research Products

    (8 results)

All 2014 2012 Other

All Journal Article (3 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results) Presentation (4 results) Remarks (1 results)

  • [Journal Article] Quantitative and in situ detection of oxidatively generated DNA damage 8,5’-cyclo-2’-deoxyadenosine using an immunoassay with a novel monoclonal antibody2014

    • Author(s)
      T. Iwamoto, P.J. Brooks, T. Nishiwaki, K. Nishimura, N. Kobayashi, S. Sugiura and T. Mori.
    • Journal Title

      Photochem. Photobiol.

      Volume: xx Issue: 4 Pages: 829-836

    • DOI

      10.1111/php.12239

    • Related Report
      2014 Annual Research Report 2013 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA損傷特異的モノクローナル抗体2012

    • Author(s)
      森俊雄、岩本顕聡
    • Journal Title

      放射線生物研究

      Volume: 47 Pages: 112-125

    • NAID

      40019392777

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Journal Article] Tmem100, an ALK1 signaling-dependent gene essential for arterial endothelium differentiation and vascular morphogenesis.2012

    • Author(s)
      染川智
    • Journal Title

      Proc. Nat. Acad. Sci. USA

      Volume: 109 Issue: 30 Pages: 12064-12069

    • DOI

      10.1073/pnas.1207210109

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] 新規モノクローナル抗体を用いた酸化的DNA損傷サイクロプリンの定量測定と可視化2014

    • Author(s)
      森 俊雄、岩本顕聡、小林信彦、杉浦重樹
    • Organizer
      日本放射線影響学会第57回大会
    • Place of Presentation
      鹿児島
    • Year and Date
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] Quantitative and in situ detection of oxidatively generated DNA damage 8,5'-cyclo-2'-deoxyadenosine using an immunoassay with a novel monoclonal antibody2014

    • Author(s)
      T. Iwamoto, P.J. Brooks, N. Kobayashi, S.Sugiura and T. Mori
    • Organizer
      16th International Congress on Photobiology
    • Place of Presentation
      Cordoba, Argentina
    • Year and Date
      2014-09-08 – 2014-09-12
    • Related Report
      2014 Annual Research Report
  • [Presentation] 新規モノクローナル抗体を用いた酸化的DNA損傷サイクロプリンの定量測定と可視化2014

    • Author(s)
      岩本顕聡、P.J. Brooks、小林信彦、杉浦重樹、森 俊雄
    • Organizer
      第36回日本光医学光生物学会
    • Place of Presentation
      大阪
    • Year and Date
      2014-07-25 – 2014-07-26
    • Related Report
      2014 Annual Research Report
  • [Presentation] Quantitative and in situ detection of oxidatively generated DNA damage 8,5'-cyclo-2'-deoxyadenosine using an immunoassay with a novel monoclonal antibody2014

    • Author(s)
      T. Iwamoto, P.J. Brooks, N. Kobayashi, S. Sugiura and T. Mori
    • Organizer
      International symposiumon xeroderma pigmentosum and related diseases: Disorders of DNA damage response-Bench to bedside-
    • Place of Presentation
      Kobe
    • Related Report
      2013 Research-status Report
  • [Remarks] ラジオアイソトープ(RI)実験施設、奈良県立医科大学

    • URL

      http://www.naramed-u.ac.jp/university/kenkyu-sangakukan/radioisotope/radioisotope.html

    • Related Report
      2014 Annual Research Report

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Published: 2013-05-31   Modified: 2019-07-29  

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