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TIGAR control myocardial energy metabolism flexibility and Apoptosis.

Research Project

Project/Area Number 24790773
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Circulatory organs internal medicine
Research InstitutionDoshisha University (2013-2014)
Kyoto Prefectural University of Medicine (2012)

Principal Investigator

MITA Yuichiro  同志社大学, 研究開発推進機構, 特別研究員 (70609122)

Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2014: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2013: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords心不全 / エネルギー代謝 / TAC / TIGAR / 糖代謝 / 糖尿病 / 圧負荷モデル
Outline of Final Research Achievements

In spite of the metabolic alterations in heart failure (HF), only recently have the mechanisms underlying these changes been identified. TIGAR reduces glycolysis, but its role on HF is unclear. To investigate the role of TIGAR, we performed TAC-operation. After 4 weeks of TAC, LV function in WT mice was decrease, but not seen in TIGAR KO mice. Next, we used TIGAR conditional KO mouse and a tamoxifen inducible KO mouse. 4 weeks after TAC, LV contraction was preserved in tamoxifen pretreated TIGARflox/flox;MerCreMer with low grade fibrosis. TIGARflox/flox;MerCreMer+ exhibited up-regulation of glucose utilization, high energy phosphate(HEP), and autophagic flux. To evaluate on late phase HF, we treated with tamoxifen 2 weeks after TAC, followed by analysis at 8 weeks. LV dysfunction was also reduced in tamoxifen mid-treated TIGARflox/flox;MerCreMer+. TIGAR attenuates adaptive response in HF. Inhibition of TIGAR improved HEP and protected from HF even after the onset of heart failure.

Report

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

    (18 results)

All 2015 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Open Access: 3 results) Presentation (13 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] An alpha-adrenergic agonist protects hearts by inducing Akt1-mediated autophagy.2015

    • Author(s)
      Nakaoka M, Iwai-Kanai E, Katamura M, Okawa Y, Mita Y, Matoba S.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 456 Issue: 1 Pages: 250-6

    • DOI

      10.1016/j.bbrc.2014.11.067

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Curcumin attenuates doxorubicin-induced cardiotoxicity by inducing autophagy via the regulation of JNK phosphorylation2014

    • Author(s)
      M Katamura, E Iwai-Kanai, M Nakaoka, Y Okawa, M Ariyoshi, Y Mita, A Nakamura, K Ikeda, T Ogata, T Ueyama, S Matoba
    • Journal Title

      J Clin Exp Cardiolog

      Volume: 5 Issue: 09 Pages: 337-337

    • DOI

      10.4172/2155-9880.1000337

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immunostaining of oxidized DJ-1 in human and mouse brains.2014

    • Author(s)
      Saito, Y., T. Miyasaka, H. Hatsuta, K. Takahashi-Niki, K. Hayashi, Y. Mita, O. Kusano-Arai, H. Iwanari, H. Ariga, T. Hamakubo, Y. Yoshida, E. Niki, S. Murayama, Y. Ihara and N. Noguchi
    • Journal Title

      J Neuropathol Exp Neurol

      Volume: 73 Issue: 7 Pages: 714-728

    • DOI

      10.1097/nen.0000000000000087

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart.2013

    • Author(s)
      Hoshino A, Mita Y, Okawa Y, Ariyoshi M, Iwai-Kanai E, Ueyama T, Ikeda K, Ogata T, Matoba S.
    • Journal Title

      Nature communications

      Volume: 4 Issue: 1 Pages: 2308-2308

    • DOI

      10.1038/ncomms3308

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] セレノプロテインPの発現・分泌に与える過酸化水素および抗酸化物質の影響2015

    • Author(s)
      三田雄一郎、斎藤芳郎、野口範子
    • Organizer
      第26回ビタミンE研究会
    • Place of Presentation
      東京
    • Year and Date
      2015-01-09 – 2015-01-10
    • Related Report
      2014 Annual Research Report
  • [Presentation] 糖尿病関連タンパク質 Selenoprotein P の発現制御機構の解析2014

    • Author(s)
      三田雄一郎、斎藤芳郎、野口範子
    • Organizer
      第 67 回日本酸化ストレス学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2014-09-04 – 2014-09-05
    • Related Report
      2014 Annual Research Report
  • [Presentation] The cellular uptake of SeP is hinhibitted by SeP specific antibodies2014

    • Author(s)
      Yuichiro Mita, Yuya Yoshioka, Yukina Nishito, Kaho Nakayama, Miki Iwasaki, Kazuhiko Takahashi, Noriko Noguchi, Yoshiro Saito
    • Organizer
      17th Biennial Meeting of Society for Free Radical Research International(SFRRI2014)
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Research-status Report
  • [Presentation] Development of new therapy of type 2 diabetes targe7ng to the insulin-resistance biomarker, Selenoprotein P2014

    • Author(s)
      Yoshiro Saito, Yuichiro Mita, Yuya Yoshioka, Kaho Nakayama, Mutsumi Tanaka, Hirofumi Misu, Toshinari Takamura, Kazuhiko Takahashi, Noriko Noguchi
    • Organizer
      17th Biennial Meeting of Society for Free Radical Research International (SFRRI2014
    • Place of Presentation
      Kyoto
    • Related Report
      2013 Research-status Report
  • [Presentation] インスリン抵抗性バイオマーカー “セレノプロテインP”の 中和抗体の探索およびin vivoでの評価 -新規2型糖尿病の治療薬創成を目指して2014

    • Author(s)
      中山 華穂、三田 雄一郎、吉岡 佑弥、西藤 有希奈、高橋 和彦、野口 範子、斎藤 芳郎
    • Organizer
      第134回日本薬学会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] G-CSFによる DOX の心筋毒性の抑制2014

    • Author(s)
      三田 雄一郎,的場 聖明,星野 温,中岡 幹彦,片村 真紀,足立 壮一,金井 恵理
    • Organizer
      第134回日本薬学会
    • Place of Presentation
      熊本
    • Related Report
      2013 Research-status Report
  • [Presentation] Study of selenium supply mechanism of selenoprotein P using 75Se and immunological methods2013

    • Author(s)
      Saito Y., Yoshioka Y., Mita Y. , Nakayama K., Nishito Y. , Takahashi K. , Noguchi N.
    • Organizer
      Study of selenium supply mechanism of selenoprotein P using 75Se and immunological methods
    • Place of Presentation
      Germany
    • Related Report
      2013 Research-status Report
  • [Presentation] Tigar (tp53-induced Glycolysis And Apoptosis Regulator) Decreases Glycogenic Energy Metabolism and Deteriorates Left Ventricular Function in Pressure Overload-induced Heart Failure Model2013

    • Author(s)
      Yoshifumi Okawa, Eri Iwai-Kanai, Yuichiro Mita, Atsushi Hoshino, Maki Katamura, Makoto Ariyoshi, Satoshi Kaimoto, Kuniyoshi Fukai, Motoki Uchihashi, Satoaki Matoba
    • Organizer
      American Heart Association (AHA) 2013 Scientific Sessions
    • Place of Presentation
      USA
    • Related Report
      2013 Research-status Report
  • [Presentation] 75Seおよび免疫学的手法を用いたセレノプロテインPのセレン運搬機構の解析2013

    • Author(s)
      吉岡 佑弥, 西藤 有希奈, 三田 雄一郎, 高橋 和彦, 野口 範子, 斎藤 芳郎
    • Organizer
      第86回日本生化学会大会
    • Place of Presentation
      横浜
    • Related Report
      2013 Research-status Report
  • [Presentation] TIGAR (TP53-induced glycolysis and apoptosis regulator) deteriorates energy metabolism in pressure overload-induced heart failure2013

    • Author(s)
      Yoshifumi Okawa, Satoaki Matoba, Eri Iwai-Kanai, Hideo Nakamura, Atsushi Hoshino, Mikihiko Nakaoka, Maki Katamura, Makoto Ariyoshi, Satoshi Kaimoto, Yuichiro Mita, Hiroaki Matsubara
    • Organizer
      第77回日本循環器病学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Granulocyte colony-stimulating factor stabilizes MDM2-p53 interaction in cardiomyocytes but not in cancer cells2013

    • Author(s)
      Yuichiro Mita, Eri Iwai-Kanai, Satoaki Matoba, Hideo Nakamura, Atsushi Hoshino, Mikihiko Nakaoka, Maki Katamura, Yoshifumi Okawa, Makoto Ariyoshi, Satoshi Kaimoto, Hiroaki Matsubara
    • Organizer
      第77回日本循環器病学会
    • Place of Presentation
      横浜
    • Related Report
      2012 Research-status Report
  • [Presentation] Inhibition of Protease Oxidation Preserves Protein Turnover of Mitochondrial Electron Transport Complex and Improves Respiration Capacity in Pressure Overload Heart Failure2012

    • Author(s)
      Atsushi Hoshino, Satoaki Matoba, Yuichiro Mita, Eri Iwai-Kanai, and Hiroaki Matsubara
    • Organizer
      AHA 2012
    • Place of Presentation
      Los Angeles, USA
    • Related Report
      2012 Research-status Report
  • [Presentation] :Granulocyte Colony-Stimulating Factor (G-CSF) Reduced Doxorubicin Induced Cardiotoxicity by Stabilizing MDM2-p53 Interaction2012

    • Author(s)
      Yuichiro Mita, Eri Iwai-Kanai, Satoaki Matoba, Hideo Nakamura, Atsushi Hoshino, Mikihiko Nakaoka, Maki Katamura, Yoshifumi Okawa, Makoto Ariyoshi, Satoshi Kaimoto, Hiroaki Matsubara
    • Organizer
      第29回ISHR日本部会総会
    • Place of Presentation
      福岡
    • Related Report
      2012 Research-status Report
  • [Patent(Industrial Property Rights)] 2型糖尿病の治療及び/又は予防薬2014

    • Inventor(s)
      斎藤芳郎、三田雄一郎、中山華穂、野口範子
    • Industrial Property Rights Holder
      斎藤芳郎、三田雄一郎、中山華穂、野口範子
    • Industrial Property Rights Type
      特許
    • Filing Date
      2014-08-18
    • Related Report
      2014 Annual Research Report

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

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