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To examine the role of Epac, a new beta-adrenergic signaling molecule, for the development of heart failure

Research Project

Project/Area Number 20590871
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionYokohama City University

Principal Investigator

OKUMURA Satoshi  Yokohama City University, 医学部, 准教授 (60233475)

Co-Investigator(Kenkyū-buntansha) SATO Motohiko  横浜市立大学, 医学部, 准教授 (40292122)
KUROTANI Reiko  横浜市立大学, 医学研究科, 特任助教 (00453043)
Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
KeywordsサイクリックAMP / シグナル伝達 / 循環器・高血圧 / 心不全 / 遺伝子改変マウス
Research Abstract

It is well known that sympathetic and thus catecholamine signal is activated thereafter to compensate cardiac dysfunction. The mechanism of such compensation by catecholamine has been traditionally understood as PKA-mediated enforcement of cardiac contractility. We hypothesized that Epac, a new target of cAMP signal that functions independently from PKA, also plays a key role. Epac1 inhibited the Jak-STAT pathway and iNOS protein in the heart in response via IL-6. Activation of the cAMP/Epac pathway protected the heart against cytokine-induced cardiac dysfunction, suggesting a new role of catecholamine signal in compensating cardiac dysfunction in endotoxemia.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (36 results)

All 2011 2010 2009 2008 Other

All Journal Article (18 results) (of which Peer Reviewed: 17 results) Presentation (13 results) Remarks (3 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by TGF・・signaling down-regulation.2011

    • Author(s)
      Kurotani R, Okumura S, Matsubara T, Yokoyama U, Buckley JR, Tomita T, Kezuka K, Nagao T, Esposito D, Tayler TE, Gillette WK, Ishikawa Y, Abe H, Ward JM, Kimura S
    • Journal Title

      J Biol Chem 386

      Pages: 19682-19692

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] The roles of cytochrome P450 in ischemic heart disease.2011

    • Author(s)
      Sato M, Yokoyama U, Fujita T, Okumura S, Ishikawa Y
    • Journal Title

      Curr Drug Metab

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of transcriptional factor E3 (TFE3) as a receptor-independent activator of G・16 : Gene regulation by nuclear G・ subunit and its activator.2011

    • Author(s)
      Sato M, Hiraoka M, Suzuki H, Bai Y, Kurotani R, Yokoyama U, Okumura S, Cismowski MJ, Lanier SM, Ishikawa Y
    • Journal Title

      J Biol Chem 286

      Pages: 17766-17776

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Identification of transcriptional factor E3 (TFE3) as a receptor-independent activator of Gα16 : Gene regulation by nuclear Gα subunit and its activator2011

    • Author(s)
      Sato M, Hiraoka M, Suzuki H, Bai Y, Kurotani R, Yokoyama U, Okumura S, Cismowski MJ, Lanier SM, Ishikawa Y
    • Journal Title

      J Biol Chem

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] The roles of cytochrome P450 in ischemic heart disease2011

    • Author(s)
      Sato M, Yokoyama U, Fujita T, Okumura S, Ishikawa Y
    • Journal Title

      Cure Drug Metab

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Secretoglobin 3A2 suppresses bleomycin-induced pulmonary fibrosis by TGFβ signaling down-regulation2011

    • Author(s)
      Kurootani R, Okumura S, Matsubara T, Yokoyama U, Buckley JR, Tomito T, Kezuka K, Nagao T, Esposito D, Tayler TE, Gillette WK, Ishikawa Y, Abe H, Ward JM, Kimura S
    • Journal Title

      J Biol Chem

      Volume: (In press)

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential roles of Epac in regulating cell death in neuronal and myocardial cells.2010

    • Author(s)
      Suzuki S, Yokoyama U, Abe T, Kiyonari H, Yamashita N, Kato Y, Kurotani R, Sato M, Okumura S, Ishikawa Y
    • Journal Title

      J Biol Chem

      Pages: 24248-24259

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus.2010

    • Author(s)
      Yokoyama U, Minamisawa S, Katayama A, Tang T, Suzuki S, Iwatsubo K, Iwasaki S, Kurotani R, Okumura S, Sato M, Yokota S, Hammond HK, Ishikawa Y
    • Journal Title

      Circ Res 106

      Pages: 1882-1892

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Caveolin gene transfer improves glucose metabolism in diabetic mice.2010

    • Author(s)
      Otsu K, Toya Y, Oshikawa J, Kurotani R, Yazawa T, Sato M, Yokoyama U, Umemura S, Minamisawa S, Okumura S, Ishikawa Y
    • Journal Title

      Am J Physiol Cell Physiol 298

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Differential regulation of vascular tone and remodeling via stimulation of type 2 and type 6 adenylyl cyclases in the ductus arteriosus2010

    • Author(s)
      Yokoyama U, Minamisawa S, Katayama A, Tang T, Suzuki S, Iwatsubo K, Iwasaki S, Kurotani R, Okumura S, Sato M, Yokota S, Hammond HK, Ishikawa Y
    • Journal Title

      Circ Res

      Volume: 106 Pages: 1882-1892

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Differential roles of Epac in regulating cell death in neuronal and myocardial cells2010

    • Author(s)
      Suzuki S, Yokoyama U, Abe T, Kiyonari H, Yamashita N, Kato Y, Kurotani R, Sato M, Okumura S, Ishikawa Y
    • Journal Title

      J Biol Chem

      Volume: 285 Pages: 24248-24259

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New aspects for the treatment of cardiac diseases based on diversity of functional controls on cardiac muscles : effects of targeted disruption of the type 5 adenylyl cyclkase gene (Review).2009

    • Author(s)
      Okumura S, Suzuki S, Ishikawa Y
    • Journal Title

      J Phramacol Sci 109

      Pages: 354-359

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Activator of G protein signaling 8 (AGS8) is required for hypoxia-induced apoptosis of cardiomyocytes : role of G・・ and connexin 43 (CX43).2009

    • Author(s)
      Sato M, Jiao Q, Honda T, Kurotani R, Toyota E, Okumura S, Takeya T, Minamisawa S, Lanier SM, Ishikawa Y
    • Journal Title

      J Biol Chem 284

      Pages: 31431-31440

    • Related Report
      2010 Final Research Report
  • [Journal Article] Caveolin gene transfer improves glucose metabolism in diabetic mice2009

    • Author(s)
      Otsu K, Toya Y, Oshikawa J, Kurotani R, Yazawa T, Sato M, Yokoyama U, Umemura S, Minamisawa S, Okumura S, Ishikawa Y
    • Journal Title

      Am J Physiol Cell physiol 298

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Actibator of G protein signaling 8(AGS8)is required for hypoxia-induced apoptosis of cardiomyocytes : role of Gβγ and connexin 43(CX43)2009

    • Author(s)
      Sato M, Jiao Q, Honda T, Kurotani R, Toyota E, Okumura S, Takeya T, Minamisawa S, Lanier SM, Ishikawa Y
    • Journal Title

      J Biol Chem 284

      Pages: 31431-31440

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] New aspects for the treatment of cardiac diseases based on the diversity of functional controls on cardiac muscles : effects of targeted disruption of the type 5 adenylyl cyclase gene2009

    • Author(s)
      Okumura S, Suzuki S, Ishikawa Y
    • Journal Title

      J Pharmacol Sci 109

      Pages: 354-359

    • NAID

      10025735009

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight.2008

    • Author(s)
      Okumura S, Tsunematsu T, Bai Y, Jiao Q, Ono S, Suzuki S, Kurotani R, Sato M, Umemura S, Minamisawa S, Ishikawa Y
    • Journal Title

      J Apply Physiol 105

      Pages: 173-179

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolicflight2008

    • Author(s)
      Okumura S, et al.
    • Journal Title

      J Apply Physiol 105

      Pages: 173-179

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Activation of Epac Signaling Protects Cardiac Myocyte from Cytokine-mediated Cardiac Dysfunction through the Inhibition of Proinflamatory Cytokine Signaling2011

    • Author(s)
      Fumika Kawamata, Satoshi Okumura, Utako Yokoyama, Yoshihiro Ishikawa
    • Organizer
      第88回日本生理学会大会
    • Related Report
      2010 Final Research Report
  • [Presentation] Activation of Epac signaling protects cardiac myocyte from cytokine-mediated cardiac dysfunction through the inhibition of proinflammatory cytokine signaling2011

    • Author(s)
      Fumika Kawamata, Satoshi Okumura, Utako Yokoyama, Yoshihiro Ishikawa
    • Organizer
      The 88^<th> Annual Meeting of the Physiological Society of Japan
    • Place of Presentation
      Yokohama in Japan(誌上開催)
    • Related Report
      2010 Annual Research Report
  • [Presentation] Pharamacological activation of type 5 adenyly1 cyclase stabilizes heart rate under microgravity induced by parabolic flight2010

    • Author(s)
      Okumura S, Bai Y, Tsunematsu T, Jin M, Jiao Q, Suzuki S, Kurotani R, Yokoyama U, Sato M, Iwatsubo K, Ishikawa Y
    • Organizer
      The 74^<th> Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Kyoto in Japan
    • Year and Date
      2010-03-07
    • Related Report
      2009 Annual Research Report
  • [Presentation] Novel transcription regulation in the hypertrophied myocardium via nuclear G・16 subunit activator G-protein signaling (AGS)2010

    • Author(s)
      Motohiko Sato, Masaharu Hiraoka, Hiroko Suzuki, Bay Yunzhe, Satoshi Okumura, Mary J. Cismowski, Stephen M. Lanier, Yoshihiro Ishikawa
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      Chicago
    • Related Report
      2010 Final Research Report
  • [Presentation] Pharmacological activation of type 5 adenylyl cyclase stabilizes heart rate under microgravity induced by parabolic flight2010

    • Author(s)
      Satoshi Okumura, Yunzhe Bai, Takashi Tsunematsu, Meihua Jin, Qibin Jiao, Sayaka Suzuki, Reiko Kurotani, Utako Yokoyama, Motohiko, Sato, Kousaku Iwatsubo, Yoshihiro Ishikawa
    • Organizer
      第74回日本循環器学会学術集会
    • Place of Presentation
      京都
    • Related Report
      2010 Final Research Report
  • [Presentation] Disruption of Epac1 Gene Preserves Cardiac Function against Pressure Overload and Chronic Catecholamine Stress2010

    • Author(s)
      Meihua Jin, Satoshi Okumura, Wenqian Cai, Yuko Hidaka, Reiko Kurotani, Utako Yokoyama, Motohiko Sato, Yoshihiro Ishikawa
    • Organizer
      第87回日本生理学会大会
    • Place of Presentation
      岩手
    • Related Report
      2010 Final Research Report
  • [Presentation] Novel transcription regulation in the hypertrophied myocardiumvia nuclear Gα16 subunit and activator of G-protein signaling (AGS)2010

    • Author(s)
      Motohiko Sato, Masaharu Hiraoka, Hiroko Suzuki, Bai Yunzhe, Satoshi Okumura, Mary J.Cismowski, Stephen M.Lanier, Yoshihiro Ishikawa
    • Organizer
      American Heart Association Scientific Scission 2010
    • Place of Presentation
      Chicago in USA
    • Related Report
      2010 Annual Research Report
  • [Presentation] Epac1 protects heart from lopopolysaccharide-induced cardiac dysfunction by inhibiting the toll-like receptor 4 signaling pathway2009

    • Author(s)
      Okumura S, Jin M, Bai Y, Suzuki S, Xuan X, Cai W, Hidaka Y, Kurotani R, Yokoyama U, Ishikawa Y
    • Organizer
      American heart Association Scientific Scission 2009
    • Place of Presentation
      Orlando in USA
    • Year and Date
      2009-11-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Activation of Epacl-specific Signaling Protects Heart from Cytokine-Mediated Cardiac Dysfunction through the inhibition of Proinflammatory Cytokine Signaling (Featured Research Scission)2009

    • Author(s)
      Okumura S, Suzuki S, Yunzhe B, Meihua J, Hidaka Y, Kurotani R, Ishikawa Y
    • Organizer
      The 73^<th> Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Osaka
    • Year and Date
      2009-03-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] Epac1 Protects Heart From Lipopolysaccharide-induced Cardiac Dysfunction By Inhibiting The Toll-like Receptor 4 Signaling Pathway2009

    • Author(s)
      Satoshi Okumura, Meihua Jin, Yunzhe Bai, Sayaka Suzuki, Xuezhe Xuan, Wenqian Cai, Yuko Hidaka, Reiko Kurotani, Utako Yokoyama, Yoshihiro Ishikawa
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      Orlando
    • Related Report
      2010 Final Research Report
  • [Presentation] Activation of Epac1-specific signaling protects heart from cytokine-mediated cardiac dysfunction through the inhibition of proinflammatory cytokine signaling2009

    • Author(s)
      Satoshi Okumura, Sayaka Suzuki, Yunzhe Bai, Meihua Jin, Reiko Kurotani, Yoshihiro Ishikawa
    • Organizer
      第73回日本循環器学会学術集会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] Activation of Epacl-specific Signaling Protects Heart from Cytokine-Mediated Cardiac Dysfunction through the inhibition of Proinflammatory Cytokine Sienaline2008

    • Author(s)
      Okumura S, Suzuki S, Yunzhe B, Meihua J, Kurotani R, Ishikawa Y
    • Organizer
      American Heart Association Scientific Sessions 2008
    • Place of Presentation
      New Orleans in USA
    • Year and Date
      2008-11-10
    • Related Report
      2008 Annual Research Report
  • [Presentation] Activation of Epac1-specific Signaling Protects Heart from Cytokine-Mediated Cardiac Dysfunction through the inhibition of Proinflammatory Cytokine Signaling.2008

    • Author(s)
      Satoshi Okumura, Sayaka Suzuki S, Yunzhe Bai, Meihua J, in, Reiko Kurotani, Yoshihiro Ishikawa
    • Organizer
      American Heart Association Scientific Sessions
    • Place of Presentation
      New Orleans
    • Related Report
      2010 Final Research Report
  • [Remarks] 横浜市立大学循環制御医学ホームページ

    • Related Report
      2010 Final Research Report
  • [Remarks] 横浜市立大学循環制御医学ホームページ

    • Related Report
      2010 Annual Research Report
  • [Remarks]

    • URL

      http://www-user.yokohama-cu.ac.jp/~seiri1/index.html

    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] アデニル酸シクラーゼの活性調節剤2010

    • Inventor(s)
      石川義弘、奥村 敏、星野雄二郎、井上誠一
    • Industrial Property Rights Holder
      横浜市立大学(60%),横浜国立大学(40%)
    • Industrial Property Number
      2010-240301
    • Filing Date
      2010-10-27
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] アデニル酸シクラーゼの活性調節剤2010

    • Inventor(s)
      石川義弘、奥村敏、星野雄二郎、井上誠一
    • Industrial Property Rights Holder
      横浜市立大学(60%),横浜国立大学(40%)
    • Industrial Property Number
      2010-240301
    • Filing Date
      2010-10-27
    • Related Report
      2010 Annual Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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