2013 Fiscal Year Final Research Report
Novel therapeutic approach for heart failure by promoting nuclear translocation of SIRT1, a protein deacetylase
| Project/Area Number |
23591085
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
TANNO Masaya 札幌医科大学, 医学部, 講師 (00398322)
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| Co-Investigator(Kenkyū-buntansha) |
MIURA Tetsuji 札幌医科大学, 医学部, 教授 (90199951)
HORIO Yoshiyuki 札幌医科大学, 医学部, 教授 (30181530)
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| Project Period (FY) |
2011 – 2013
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| Keywords | 心不全 / SIRT1 / 酸化ストレス / 糖尿病 / 細胞死 |
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| Research Abstract |
Nuclear translocation of SIRT1 suppresses cardiomyocyte death in failing hearts. We demonstrated that phosphorylation of Ser517 of SIRT1 by Akt/PI3K contributed to the nuclear translocation. Furthermore, we identified proteins whose binding to SIRT1 change during oxidative stress, using immunoprecipitation, 2D gel electrophoresis and mass spectrometry. The physiological significance of the protein-protein interaction is currently under investigation. To translate the cardioprotective function of activation or nuclear translocation of SIRT1, we first analyzed a characteristics of OLETF rats, obese insulin-resistant type 2 diabetes rats, as an in vivo animal model for heart failure. In this model, diastolic dysfunction was induced under pressure overload, but not physiological conditions, and the mechanisms that trigger the functional impairment was explored in detail. We are currently investigating whether and how SIRT1 modifies the development of diastolic dysfunction.
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[Journal Article] Role of ER Stress in Ventricular Contractile Dysfunction in Type 2 Diabetes2012
Author(s)
Takada A, Miki T, Kuno A, Kouzu H, Sunaga D, Itoh T, Tanno M, Yano T, Sato T, Ishikawa S, Miura T
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Journal Title
PLoS One
Volume: 7
Pages: e39893
DOI
Peer Reviewed
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[Journal Article] Histopathology of the pancreas in fulminant type 1 diabetes after 23-year follow-up : a case report2012
Author(s)
Sato T, Miki T, Murakami N, Hirohashi Y, Kouzu H, Furuhashi M, Tanno M, Yuda T, Saitoh S, Hasegawa T, Miura T
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Journal Title
Pathology International
Volume: 62
Pages: 827-29
DOI
Peer Reviewed
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[Presentation] Activation of the glucagon-like peptide-1 receptor restores myocardial autophagic flux and reduces mortality after myocardial infarction in diabetic rats2013
Author(s)
Murase H, Kuno A, Miki T, Tanno M, Yano T, Kouzu H, Tobisawa T, Ogasawara M, Ishikawa S, Miura T
Organizer
American Heart Association 2013
Place of Presentation
Dallas, TX, U.S.A.
Year and Date
2013-11-17
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[Presentation] Activation of the mitochondrial ATP-sensitive potassium channel achieves cell protection by promoting re-closure of the mPTP via suppression of GSK-3β-complex III interaction2013
Author(s)
Tanno M, Sunaga D, Miki T, Kuno A, Kouzu H, Sato T, Ishikawa S, Ogasawara M, Tobisawa T, Miura T
Organizer
European Society of Cardiology Congress 2013
Place of Presentation
Amsterdam, Netherlands
Year and Date
2013-09-03
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[Presentation] Type 2 diabetes induces ventricular electrical remodeling with a transmural gradient2013
Author(s)
Tobisawa T, Sato T, Yuda S, Miki T, Tanno M, Kuno A, Kobayashi T, Akasaka H, Tohse N, Miura T
Organizer
European Society of Cardiology Congress 2013
Place of Presentation
Amsterdam, Netherlands
Year and Date
2013-09-02
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[Presentation] Mechanisms underlying mitochondrial translocation of GSK-3β, a crucial inducer of mitochondrial permeability transition : GSK-3βactivity, interaction with VDAC2 and a mitochondrial targeting sequence2013
Author(s)
Tanno M, Kuno A, Ishikawa S, Ogasawara M, Tobisawa T, Murase H, Sato T, Kouzu H, Miki T, Miura T
Organizer
Basic Cardiovascular Sciences 2013 (AHA)
Place of Presentation
Las Vegas, NV, U.S.A.
Year and Date
2013-07-23
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[Presentation] Type 2 diabetes induces subendocardium-predominant reduction of transient outward K+ current via downregulation of Kv4.2 and KChIP22013
Author(s)
Sato T, Kobayashi T, Kuno K, Murase H, Kouzu H, Tanno T, Miki T, Miura T, Tohse N
Organizer
The 50th International Society of Heart Research Japanese Section
Place of Presentation
San Diego, CA, U.S.A.
Year and Date
2013-06-29
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