anti-atherosclerotic and anti-cancer effects of AMPK activation
Project/Area Number |
26461108
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Cardiovascular medicine
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Research Institution | Osaka University |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
朝野 仁裕 大阪大学, 医学系研究科, 講師 (60527670)
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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)
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Research Collaborator |
Yan Yi 大阪大学, 大学院医学系研究科, 大学院生
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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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)
|
Keywords | AMPK / 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.
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] A Development of Nucleic Chromatin Measurements as a New Prognostic Marker for Severe Chronic Heart Failure2016
Author(s)
38.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.
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Journal Title
PLoS One
Volume: 11
Pages: e0148209
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Btg2 is a Negative Regulator of Cardiomyocyte Hypertrophy through a Decrease in Cytosolic RNA.2016
Author(s)
39.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.
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Journal Title
Sci Rep.
Volume: 6
Pages: 28592
DOI
Related Report
Peer Reviewed
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[Journal Article] Identification of the Mtus1 Splice Variant as a Novel Inhibitory Factor Against Cardiac Hypertrophy.2016
Author(s)
40.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.
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Journal Title
J Am Heart Assoc.
Volume: 5
Pages: e003521
DOI
Related Report
Peer Reviewed
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[Journal Article] Augmented AMPK activity inhibits cell migration by phosphorylating the novel substrate Pdlim52015
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
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Journal Title
Nature Communications
Volume: 6
Pages: 6137
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Higd1a is a positive regulator of cytochrome c oxidase.2015
Author(s)
.Hayashi T, Asano Y, Shintani Y, Aoyama H, Kioka H, Tsukamoto O, Hikita M, Shinzawa-Itoh K, Takafuji K, Higo S, Kato H, Yamazaki S, Matsuoka K, Nakano A, Asanuma H, Asakura M, Minamino T, Goto Y, Ogura T, Kitakaze M, Komuro I, Sakata Y, Tsukihara T, Yoshikawa S, Takashima S.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 112
Pages: 1553
DOI
Related Report
Peer Reviewed
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[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.
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Journal Title
J Clin Invest.
Volume: 124
Pages: 2464
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Noninvasive and quantitative live imaging reveals a potential stress-responsive enhancer in the failing heart.2014
Author(s)
31.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.
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Journal Title
FASEB J.
Volume: 28
Pages: 1870
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Evaluation of intramitochondrial ATP levels identifies G0/G1 switch gene 2 as a positive regulator of oxidative phosphorylation.2014
Author(s)
30.Kioka H, Kato H, Fujikawa M, Tsukamoto O, Suzuki T, Imamura H, Nakano A, Higo S, Yamazaki S, Matsuzaki T, Takafuji K, Asanuma H, Asakura M, Minamino T, Shintani Y, Yoshida M, Noji H, Kitakaze M, Komuro I, Asano Y, and Takashima S.
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Journal Title
Proc Natl Acad Sci U S A.
Volume: 111
Pages: 273
DOI
Related Report
Peer Reviewed / Open Access
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