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anti-atherosclerotic and anti-cancer effects of AMPK activation

Research Project

Project/Area Number 26461108
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Cardiovascular medicine
Research InstitutionOsaka University

Principal Investigator

Tsukamoto Osamu  大阪大学, 医学系研究科, 助教 (80589151)

Co-Investigator(Kenkyū-buntansha) 朝野 仁裕  大阪大学, 医学系研究科, 講師 (60527670)
Co-Investigator(Renkei-kenkyūsha) SHINTANI Yasunori  大阪大学, 大学院医学系研究科, 助教 (20712243)
HIGO Shuichiro (KATO Hisakazu)  大阪大学, 大学院医学系研究科, 助教 (00604034)
Research Collaborator Yan Yi  大阪大学, 大学院医学系研究科, 大学院生
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
KeywordsAMPK / PDLIM5 / cell migration / AMPK / cell migration / AMPキナーゼ / Pdlim5 / 細胞遊走
Outline of Final Research Achievements

We identified Pdlim5 as a novel AMPK substrate. AMPK phosphorylates Pdlim5 at Ser177. To investigate the role of Ser177 phosphorylation by AMPK, we produced the knockdown-and-rescue (KDR) system of vSMCs, in which endogenous Pdlim5 were replaced by exogenous EGFP-tagged-Pdlim5s. KDR/S177D-Pdlim5 cells exhibited perturbed cell migration compared with KDR/wild-type- and KDR/S177A-Pdlim5 cells even in the absence of AMPK activator. Furthermore, KDR/S177D-Pdlim5 cells exhibited defective lamellipodia formation. Consistent with this, KDR/S177D-Pdlim5 cells exhibited dislocation of Arp2/3 complex from the leading edge to cytosol and suppressed Rac1 activity. Finally, KDR/S177D-Pdlim5 cells disrupted the physical association with Arhgeg6, a guanine nucleotide exchange factor for Rac1. In conclusion, enhanced AMPK activation inhibits cell migration by interfering lamellipodia formation by suppressing the Arhgef6-Rac1-Arp2/3 signaling pathway via phosphorylating Pdlim5.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • 2014 Research-status Report
  • Research Products

    (12 results)

All 2016 2015 2014 2013 Other

All Journal Article (11 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 11 results,  Open Access: 8 results,  Acknowledgement Compliant: 4 results) Remarks (1 results)

  • [Journal Article] A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure.2016

    • Author(s)
      Kanzaki M, Asano Y, Ishibashi-Ueda H, Oiki E, Nishida T, Asanuma H, Kato H, Oka T, Ohtani T, Tsukamoto O, Higo S, Kioka H, Matsuoka K, Sawa Y, Komuro I, Kitakaze M, Takashima S, Sakata Y.
    • Journal Title

      PLoS One.

      Volume: 11 Issue: 2 Pages: e0148209-e0148209

    • DOI

      10.1371/journal.pone.0148209

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA.2016

    • Author(s)
      Masumura Y, Higo S, Asano Y, Kato H, Yan Y, Ishino S, Tsukamoto O, Kioka H, Hayashi T, Shintani Y, Yamazaki S, Minamino T, Kitakaze M, Komuro I, Takashima S, Sakata Y.
    • Journal Title

      Sci Rep.

      Volume: 6 Issue: 1 Pages: 28592-28592

    • DOI

      10.1038/srep28592

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy.2016

    • Author(s)
      Ito S, Asakura M, Liao Y, Min KD, Takahashi A, Shindo K, Yamazaki S, Tsukamoto O, Asanuma H, Mogi M, Horiuchi M, Asano Y, Sanada S, Minamino T, Takashima S, Mochizuki N, Kitakaze M.
    • Journal Title

      J Am Heart Assoc.

      Volume: 5 Issue: 7

    • DOI

      10.1161/jaha.116.003521

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim5.2015

    • Author(s)
      Yan Y, Tsukamoto O, Nakano A, Kato H, Kioka H, Ito N, Higo S, Yamazaki S, Shintani Y, Matsuoka K, Liao Y, Asanuma H, Asakura M, Takafuji K, Minamino T, Asano Y, Kitakaze M, Takashima S.
    • Journal Title

      Nat Commun.

      Volume: 6 Issue: 1 Pages: 6137-6137

    • DOI

      10.1038/ncomms7137

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Higdla is a oositive regulaator of cytochrome c oxidase2015

    • Author(s)
      T. Hayashi, Y. Asano, Y. Shintani, H. Aoyama, H. Kioka, O. Tsukamoto, M. Hikita, K. Shinzawa-Itoh, K. Takajuji, S. Higo, H. Kato, S. Yamazaki, K. Matsuoka, A. Nakano, H. Asanuma, M. Asakura, T. Minamino, Y. Goto, T. Ogura, M. Kitakaze, I. Komuro, Y. Sakata, T. Tsukihara, S. Yoshikawa, S. Takashima
    • Journal Title

      Proc. Nat. Acad. Sci. U.S.A.

      Volume: 112 Issue: 5 Pages: 1553-1558

    • DOI

      10.1073/pnas.1419767112

    • Related Report
      2015 Research-status Report 2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different Implications of Functional Tricuspid Regurgitation Between Heart Failure (HF) With Reduced Ejection Fraction (EF) and HF With Preserved EF2015

    • Author(s)
      Tsukamoto O, Kitakaze M
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 7 Pages: 1448-1449

    • DOI

      10.1253/circj.CJ-15-0560

    • NAID

      130005083967

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Recent Progress and Next Challenges in the Treatment of Symptomatic Heart Failure in Japan2015

    • Author(s)
      Tsukamoto O, Kitakaze M
    • Journal Title

      Circulation Journal

      Volume: 79 Issue: 11 Pages: 2322-2323

    • DOI

      10.1253/circj.CJ-15-1014

    • NAID

      130005104913

    • ISSN
      1346-9843, 1347-4820
    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] Targeting lysosomal Ca2+ to reduce reperfusion injury.2015

    • Author(s)
      Tsukamoto O, Asanuma H, Kitakaze M.
    • Journal Title

      Cardiovasc Res

      Volume: 108 Issue: 3 Pages: 321-323

    • DOI

      10.1093/cvr/cvv242

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Journal Article] PDE5 inhibitor efficacy is estrogen dependent in female heart disease.2014

    • Author(s)
      32.Sasaki H, Nagayama T, Blanton RM, Seo K, Zhang M, Zhu G, Lee DI, Bedja D, Hsu S, Tsukamoto O, Takashima S, Kitakaze M, Mendelsohn ME, Karas RH, Kass DA, Takimoto E.
    • Journal Title

      J Clin Invest.

      Volume: 124 Issue: 6 Pages: 2464-2464

    • DOI

      10.1172/jci70731

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart.2014

    • Author(s)
      Matsuoka K, Asano Y, Higo S, Tsukamoto O, Yan Y, Yamazaki S, Matsuzaki T, Kioka H, Kato H, Uno Y, Asakura M, Asanuma H, Minamino T, Aburatani H, Kitakaze M, Komuro I, Takashima S.
    • Journal Title

      FASEB J.

      Volume: 28(4) Issue: 4 Pages: 1870-9

    • DOI

      10.1096/fj.13-245522

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Evaluation of intra-mitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation2013

    • Author(s)
      Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Tkafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y and Takashima S
    • Journal Title

      PNAS

      Volume: 111 Issue: 1 Pages: 273-278

    • DOI

      10.1073/pnas.1318547111

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access
  • [Remarks] 細胞遊走を制御する蛋白質を同定

    • URL

      http://medbio.sakura.ne.jp/cms/wp-content/uploads/2015/02/6ba705b56624d11b034d9b434b1bc0e8.pdf

    • Related Report
      2014 Research-status Report

URL: 

Published: 2014-04-04   Modified: 2018-03-22  

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