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Biomarkers for ischemia and renal faiure

Research Project

Project/Area Number 24659062
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionTohoku University

Principal Investigator

ABE Takaaki  東北大学, 医工学研究科, 教授 (80292209)

Project Period (FY) 2012-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords1-メチルアデノシン / 修飾核酸 / 急性虚血 / 腎機能障害 / 酸化ストレス / 腎不全物質 / メタボローム解析 / LC/MS/MS
Research Abstract

Tissue damage by oxidative stress is a key pathogenic mechanism in various diseases including acute kidney injury and chronic kidney disease. Its early detection is important. Using a tRNA-specific modified nucleoside 1-methyladenosine (m1A) antibody, we demonstrate oxidative stress induces direct conformational change in tRNA structure and the change promotes subsequent tRNA fragmentation. Such tRNA changes occur much earlier than DNA damage. By various types of tissue damage model (ischemic reperfusion, toxic injury), the circulating tRNA-derivative levels are increased and the increase is more rapid than the known damage markers. In humans, the circulating tRNA-derivatives also increase under renal ischemia conditions. It also correlates with mortality in the general population (n=1,033 for 6.7 year follow up) . Therefore, tRNA damage reflects early oxidative stress damage and its detection is a useful tool for identifying organ damages and forming a clinical prognosis.

Report

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

    (20 results)

All 2014 2013 2012 Other

All Journal Article (7 results) (of which Peer Reviewed: 7 results) Presentation (8 results) Remarks (1 results) Patent(Industrial Property Rights) (4 results) (of which Overseas: 2 results)

  • [Journal Article] Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage with Prognostic Significance2014

    • Author(s)
      Mishima E., Inoue C., Saigusa D., Inoue R., Ito K., Ito S., Tomioka Y., Itoh K. and Abe T.
    • Journal Title

      J . Am. Soc. Nephrol.

      Volume: pii : ASN (Epub ahead of print) Pages: 2013091001-2013091001

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Conformational Change in tRNA is an Early Indicator of Acute Cellular Damage2014

    • Author(s)
      Mishima E.
    • Journal Title

      J. Am. Soc. Nephrol.

      Volume: 確定

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl Sulfate Down-Regulates SLCO4C1 Transporter through Up-Regulation of GATA32013

    • Author(s)
      Akiyama Y, Kikuchi K, Saigusa D, Suzuki T, Takeuchi Y, Mishima E, Yamamoto Y, Ishida A, Sugawara D, Jinno D, Shima H, Toyohara T, Suzuki C, Souma T, Moriguchi T, Tomioka Y, Ito S, Abe T.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 7 Pages: e66518-e66518

    • DOI

      10.1371/journal.pone.0066518

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Mutation of the Mg^(2+) Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype.2013

    • Author(s)
      Hurd TW, Otto EA, Mishima E, Gee HY, Inoue H, Inazu M, Yamada H, Halbritter J, Seki G, Konishi M, Zhou W, Yamane T, Murakami S, Caridi G, Ghiggeri G, Abe T, Hildebrandt F
    • Journal Title

      J Am Soc Nephrol.

      Volume: 24 Issue: 6 Pages: 967-977

    • DOI

      10.1681/asn.2012101034

    • Related Report
      2013 Final Research Report
    • Peer Reviewed
  • [Journal Article] Indoxyl sulfate down-regulates SLCO4C1 transporter through up-regulation of GATA2013

    • Author(s)
      Akiyama Y.
    • Journal Title

      Plos One

      Volume: 8

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutation of the Mg2+ Transporter SLC41A1 Results in a Nephronophthisis-Like Phenotype.2013

    • Author(s)
      Hurd TW
    • Journal Title

      J. Am. Soc. Nephrol.

      Volume: 24 Pages: 967-977

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A metabolomic approach to clarifying the effect of AST-120 on 5/6 nephrectomized rats by capillary electrophoresis with mass spectrometry (CE-MS).2012

    • Author(s)
      Akiyama Y.
    • Journal Title

      Toxins

      Volume: 4 Issue: 11 Pages: 1309-1322

    • DOI

      10.3390/toxins4111309

    • Related Report
      2012 Research-status Report
    • Peer Reviewed
  • [Presentation] CE-MSを用いた透析患者の病態に特有な尿毒症物質の同定2013

    • Author(s)
      秋山泰利
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-12
    • Related Report
      2013 Final Research Report
  • [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定(その1)2013

    • Author(s)
      佐原利人
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-12
    • Related Report
      2013 Final Research Report
  • [Presentation] エリスロポエチン産生を増強させる化合物群の探索と同定(その2)2013

    • Author(s)
      鈴木雄介
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-12
    • Related Report
      2013 Final Research Report
  • [Presentation] tRNAの挙動検知はDNAダメージよりも早期の虚血組織障害マーカーとなる2013

    • Author(s)
      三島英換
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Year and Date
      2013-05-10
    • Related Report
      2013 Final Research Report
  • [Presentation] Renoprotective effects of statin in patients with chronic kidney disease2012

    • Author(s)
      Suzuki T, Saigusa D, Mishima E, Akiyama Y, Takeuchi Y, Sato H, Ito S, Abe T
    • Organizer
      Renal week 2012, ASN
    • Place of Presentation
      San Diego, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] Identifying the Uremic Compounds Specifically Involved in the Pathophysiology of Hemodialysis Patients by Capillary Electrophoresis-Mass Spectrometry2012

    • Author(s)
      Akiyama Y, Takeuchi Y, Mishima E, Suzuki T, Ito S, Soga T, Abe T
    • Organizer
      Renal week 2012, ASN
    • Place of Presentation
      San Diego, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] 三島 英換 tRNAの挙動検知はDNAダメージよりも早期の虚血組織障害マーカーとなる

    • Author(s)
      三島 英換
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Presentation] CE-MSを用いた透析患者の病態に特異的な尿毒症物質の同定

    • Author(s)
      秋山 泰利
    • Organizer
      第56回日本腎臓学会学術総会
    • Place of Presentation
      東京国際フォーラム
    • Related Report
      2013 Annual Research Report
  • [Remarks]

    • URL

      http://plaza.umin.ac.jp/~takaabe/

    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] 腎機能障害の予防又は改善剤2013

    • Inventor(s)
      阿部 高明
    • Industrial Property Rights Holder
      阿部 高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-04
    • Related Report
      2013 Final Research Report
  • [Patent(Industrial Property Rights)] エリスロポエチン産生促進剤2013

    • Inventor(s)
      阿部 高明
    • Industrial Property Rights Holder
      阿部 高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-25
    • Related Report
      2013 Final Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 腎機能障害の予防又は改善剤2013

    • Inventor(s)
      阿部高明
    • Industrial Property Rights Holder
      阿部高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-10-04
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] エリスロポエチン産生促進剤2013

    • Inventor(s)
      阿部高明
    • Industrial Property Rights Holder
      阿部高明
    • Industrial Property Rights Type
      特許
    • Filing Date
      2013-11-25
    • Related Report
      2013 Annual Research Report
    • Overseas

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

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