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Molecular mechanism of autonomic regulation of cardiac function

Research Project

Project/Area Number 19390217
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

ISHIKAWA Yoshihiro  Yokohama City University, 医学研究科, 教授 (40305470)

Co-Investigator(Kenkyū-buntansha) SATO Motohiko  横浜市立大学, 医学部, 准教授 (40292122)
OKUMURA Satoshi  横浜市立大学, 医学部, 准教授 (60233475)
南沢 享  横浜市立大学, 医学研究科, 客員教授 (40257332)
Co-Investigator(Renkei-kenkyūsha) MINAMISAWA Susumu  横浜市立大学, 医学研究科, 客員教授 (40257332)
Project Period (FY) 2007 – 2008
Project Status Completed (Fiscal Year 2008)
Budget Amount *help
¥18,720,000 (Direct Cost: ¥14,400,000、Indirect Cost: ¥4,320,000)
Fiscal Year 2008: ¥8,840,000 (Direct Cost: ¥6,800,000、Indirect Cost: ¥2,040,000)
Fiscal Year 2007: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords心臓病態学 / 自律神経 / 心機能 / cAMP / カテコラミン / 分子 / 心臓 / 心不全 / ダウンレギュレーション
Research Abstract

心臓に発現するアデニル酸シクラーゼサブタイプの生理的意義を、ノックアウト動物などの遺伝子操作、サブタイプ特異的作動薬などの薬理学的手法を用いて、心機能制御に及ぼす影響を中心に検討した。とくに近年になってcAMPシグナルの新しい下流蛋白として同定されたEpacと呼ばれる制御蛋白を中心にアデニル酸シクラーゼサブタイプとの連関を中心に検討した。本申請は、心機能の最大の制御メカニズムである自律神経調節の分子メカニズムの解明であり、交感神経刺激は心機能の最大の調節因子であることは数十年にわたって認識されてきたが、本研究によって、その分子メカニズムがcAMPによるシグナルネットワークの制御として解明されつつある。

Report

(3 results)
  • 2008 Annual Research Report   Final Research Report ( PDF )
  • 2007 Annual Research Report
  • Research Products

    (35 results)

All 2008 2007 Other

All Journal Article (23 results) (of which Peer Reviewed: 19 results) Presentation (9 results) Remarks (3 results)

  • [Journal Article] Type 5 adenylyl cyclase plays a major role in stabilizing heart rate in response to microgravity induced by parabolic flight2008

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

      J Appl Physiol 105

      Pages: 173-179

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Sarcalumenin alleviates stress-induced cardiac dysfunction by improving Ca2+ handling of the sarcoplasmic reticulum2008

    • Author(s)
      Shimura M, et.al.
    • Journal Title

      Cardiovasc Res 77

      Pages: 362-370

    • Related Report
      2008 Final Research Report
  • [Journal Article] Epac 1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration2008

    • Author(s)
      Yokoyama U, et.al.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol 295

    • Related Report
      2008 Final Research Report
  • [Journal Article] PGE2-activated Epac promotes neointimal cushin formation of the rat ductus arteriosus by a process distinct from that of PKA2008

    • Author(s)
      Yokoyama U, et.al.
    • Journal Title

      J. Biol. Chem 283

      Pages: 28702-28709

    • Related Report
      2008 Final Research Report
  • [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, et al.
    • Journal Title

      J Appl Physiol. 105

      Pages: 173-179

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Sarcalumenin alleviates stress-induced cardiac dysfunction by improving Ca2+ handling of the sarcoplasmic reticulum.2008

    • Author(s)
      Shimura M, et al.
    • Journal Title

      Cardiovasc Res 77

      Pages: 362-370

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Caveolin-3 expression and caveolae are required for isoflurane-induced cardiac protection from hypoxia and ischemia/reperfusion injury.2008

    • Author(s)
      Horikawa Y, et al.
    • Journal Title

      J. Mol. Cell. Cardiol 44

      Pages: 123-130

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Epacl is upregulated during neointima formation and promotes vascular smooth muscle cell migration. :2008

    • Author(s)
      Yokoyama U, et al.
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol. 295

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A case of giant coronary aneurysm and literature review.2008

    • Author(s)
      Ebina T, et al.
    • Journal Title

      J. Cardiol. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] PGE2-activated Epac promotes neointimal cushin formation of the rat ductus arteriosus by a process distinct from that of PKA2008

    • Author(s)
      Yokoyama U, et al.
    • Journal Title

      J. Biol. Chem. 283

      Pages: 28702-28709

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cardiac specific overexpression of caveolin-3 induces endogenous cardiac protection by mimicking ischemic predoncitioning.2008

    • Author(s)
      TsutsumiY, et al.
    • Journal Title

      Circulation 118

      Pages: 1979-88

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A cyclic AMP pathway selectively required for reward prediction.2008

    • Author(s)
      Kheirbek MA, et al.
    • Journal Title

      J. Neurosci 28

      Pages: 11401-11408

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy2007

    • Author(s)
      Ulucan C, Wang X, Baljinnyam E, Bai Y-Z, Okumura S, Sato M, Minamisawa S, Hirotani S, and Ishikawa Y
    • Journal Title

      Am.J.Physiol.Heart Circ.Physiol 293

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Dopamine induces apoptosis in young, but not in neonatal, neurons via Ca(2+)-dependent signal, Am2007

    • Author(s)
      Iwatsubo K, Suzuki S, Li C, Tsunematsu T, Nakamura F, Okumura S, Sato M, Minamisawa S, Toya Y, Umemura S, and Ishikawa Y
    • Journal Title

      J.Physiol. Cell.Physiol 293

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-selective regulation of adenylyl cyclase by forskolin derivatives : Prediction of selectivity by computer-based analysis2007

    • Author(s)
      Eguchi H, Iwatsubo K, and Ishikawa Y
    • Journal Title

      Letters in Drug Design & Discovery 4

      Pages: 434-441

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of Type 5 adenylyl cyclase enhances desensitization of the cyclic adenosine monophsphate signal and icreases the Akt signal with chronic catecholamine stress2007

    • Author(s)
      Okumura S, Vanter DE, Kurotani R, Bai Y, Gao S, Yuan Z, Iwatsubo K, Ulucan C, Kawabe J, Ghosh K, Vanter FS, and Ishikawa Y
    • Journal Title

      Circulation 116

      Pages: 1776-1783

    • Related Report
      2008 Final Research Report
    • Peer Reviewed
  • [Journal Article] Developmental changes in gene expression of Epac and its upregulation in myocardial hypertrophy.2007

    • Author(s)
      Ulucan C, Wang X, Baljinnyam E, Bai Y-Z, Okumura S, Sato M, Minamisawa S, Hirotani S, and Ishikawa Y
    • Journal Title

      Am. J. Physiol. Heart Circ. Physiol. 293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dopamine induces apoptosis in young, but not in neonatal, neurons via Ca(2+)-dependent signal.2007

    • Author(s)
      Iwatsubo K, Suzuki S, Li C, Tsunematsu T, Nakamura F, Okumura S, Sato M, Minamisawa S, Toya Y, Umemura S, and Ishikawa Y
    • Journal Title

      Am. J. Physiol. Cell. Physiol. 293

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Isoform-selective regulation of adenylyl cyclase by forskolin derivatives: Prediction of selectivity by computer-based analysis.2007

    • Author(s)
      Eguchi H, Iwatsubo K, and Ishikawa Y
    • Journal Title

      Letters in Drug Design & Discovery 4

      Pages: 434-441

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Interleukin-15 Inhibits Smooth Muscle Cell Proliferation and Hyaluron an Production in Rat Ductus Arteriosus.2007

    • Author(s)
      Iwasaki S, Minamisawa S, Yokoyama U, Akaike T, Quan H, Nagashima Y, Nishimaki S, Ishikawa Y, and Yokota S
    • Journal Title

      Pediatr. Res. 62

      Pages: 392-398

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disruption of Type 5 adenylyl cyclase enhances desensitization of the cyclic adenosine monophsphate signal and increases the Akt signal with chronic catecholamine stress.2007

    • Author(s)
      Okumura S, Vatner DE, Kurotani R, Bai Y, Gao S, Yuan Z, Iwatsubo K, Ulucan C, Kawabe J, Ghosh K, Vatner FS, and Ishikawa Y
    • Journal Title

      Circulation 116

      Pages: 1776-1783

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Maternal vitamin A alters gene profiles and structural maturation of the rat ductus arteriosus.2007

    • Author(s)
      Yokoyama U, Sato Y, Akaike T, Ishida S, Sawada J, Nagao T, Quan H, Jin M, Iwamoto M, Yokota S, Ishikawa Y, and Minamisawa S
    • Journal Title

      Physiol. Genomics 31

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 成熟マウス線条体培養法の確立とcAMPシグナルによる細胞死の検討2007

    • Author(s)
      鈴木さやか、岩坪耕策、Ulucan Coskun, 常松尚志、石川義弘
    • Journal Title

      日本病態生理学会雑誌

      Pages: 26-43

    • Related Report
      2007 Annual Research Report
  • [Presentation] An Involvement of a Novel G-protein Activator on Hypoxia-Induced Apoptosis of Cardiomyocytes and its Interaction with Connexin 432008

    • Author(s)
      Sato M, et.al.
    • Organizer
      American Heart Association's Scientific Sessions 2008
    • Place of Presentation
      New Orleans
    • Related Report
      2008 Final Research Report
  • [Presentation] Activation of Epac1-specific Signaling Protects Heart form Cytokine-Mediated Cardiac Dysfunction through the inhibition of Proinflammatory Cytokine Signaling(Oral presentation)2008

    • Author(s)
      Okumura S, et.al.
    • Organizer
      American Heart Association's Scientific Sessions 2008
    • Place of Presentation
      New Orleans
    • Related Report
      2008 Final Research Report
  • [Presentation] Sarcalumenin plays a critical role in age-dependent reduction in cardiac function and SERCA2a activity2008

    • Author(s)
      Qibin J, et.al.
    • Organizer
      Experimental Biology
    • Place of Presentation
      San Diego
    • Related Report
      2008 Final Research Report
  • [Presentation] An Involvement of a Novel G-protein Activator on Hypoxia-Induced Apoptosis of Cardiomyocytes and its Interaction with Connexin 43.2008

    • Author(s)
      Sato M, et al
    • Organizer
      American Heart Association's Scientific Sessions2008
    • Place of Presentation
      New Orleans
    • Related Report
      2008 Annual Research Report
  • [Presentation] Activation of Epacl-specific Signaling Protects Heart from Cytokine-Mediated Cardiac Dysfunction through the inhibition of Proinflammatory Cytokine Sienaling(Oral presentation).2008

    • Author(s)
      Okumura S, et al
    • Organizer
      American Heart Association Scientific Sessions2008
    • Place of Presentation
      New Orleans
    • Related Report
      2008 Annual Research Report
  • [Presentation] Sarcalumenin plays a critical role in age-dependent reduction in cardiac function and SERCA2a activity .2008

    • Author(s)
      Qibin J, et al
    • Organizer
      Experimental Biology
    • Place of Presentation
      San Diego
    • Related Report
      2008 Annual Research Report
  • [Presentation] Disruption of type 5 adenylyl cyclase preserves cardiac function against chronic catecholamine stress2007

    • Author(s)
      Okumura S, Minamisawa S, Ishikawa Y
    • Organizer
      第11回日本心不全学会
    • Place of Presentation
      東京
    • Related Report
      2008 Final Research Report 2007 Annual Research Report
  • [Presentation] Epac1 promotes intimal cushion formation of the rat ductus arteriosus by enhancing smooth muscle cell migration2007

    • Author(s)
      赤池徹, 横山詩子, 全紅, 岩本眞理, 石川義弘, 南沢享
    • Organizer
      第71回日本循環器学会総会
    • Place of Presentation
      神戸
    • Related Report
      2008 Final Research Report
  • [Presentation] 虚血心筋に発現する新たなG蛋白活性調整因子の同定2007

    • Author(s)
      佐藤元彦, 本多崇, ラニアー ステファン,豊田英嗣, シスモウスキー マリー, スマッカ アラン, チリアン ウィリアム, 石川義弘
    • Organizer
      第84回日本生理学会大会
    • Place of Presentation
      大阪
    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2008 Final Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2008 Annual Research Report
  • [Remarks]

    • URL

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

    • Related Report
      2007 Annual Research Report

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Published: 2007-04-01   Modified: 2016-04-21  

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