• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2007 Fiscal Year Final Research Report Summary

Subtype specific cardiac regulation by adenylyl cyclase and its application for the treatment of heart failure by specific ihhibitor

Research Project

Project/Area Number 16590719
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 (2006-2007)
Nippon Medical School (2004-2005)

Principal Investigator

OKUMURA Satoshi  Yokohama City University, Graduate School of Medicine, Associate Professor (60233475)

Co-Investigator(Kenkyū-buntansha) ISHIKAWA Tfbshihiro  Yokohama City University, Graduate School of Medicine, Professor (40305470)
SATO Naoki  Nippon Medical School, 医学部, Assitant Professor (70291721)
Project Period (FY) 2004 – 2007
Keywordsadenylyl cyclase / knockout mouse / isoproterenol / desensitization / mRNA
Research Abstract

Desensitization of the cAMP signal is a protective mechanism against catecholamine stress on cardiac myocytes to prevent the development of apoptosis. Molecular mechanisms of desensitization have been well studied at the level of receptors, but poorly at the level of the effector enzyme, adenylyl cyclase. To examine the role of type 5 adenylyl cyclase (AC), a major cardiac isoform, in desensitization and apoptosis, we examined the effects of chronic isoproterenol (ISO) infusion in type 5 adenylyl cyclase-null mice (AC5KO) and wild type controls (WT) Desensitization was more effective in AC5KO after infusion, as reflected by a greater degree of downregulation of AC catalytic activity after infusion. WT showed resistance to such desensitization because the type 5 isoform protein expression underwent paradoxical upregulation. The number of apoptotic myocytes was similar at baseline, but significantly smaller in AC5KO after infusion. This was accompanied by a 4-fold greater increase in Bcl-2 and a 3-fold greater increase in phospho-Akt in AC5KO. The latter is most likely through increased membrane localization of PDK1 (phosphoinositide-dependent protein kinase 1), which is known to be inhibited by the CAMP signal. Thus, the property of AC5KO, i.e., enhanced desensitization and protection against apoptosis, suggests that isoform-specific inhibition of type 5 AC may be beneficial following chronic catecholamine stress, and potentially in the treatment of heart failure.

  • Research Products

    (21 results)

All 2008 2007 2006 2005

All Journal Article (8 results) (of which Peer Reviewed: 4 results) Presentation (13 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 (in press)

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Type 5 adenylyl cyclase plays a maj or role in stabilizing heart rate in response to microgravity induced by parabolic flight2008

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

      J Appl Physiol (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Disruption of type 5 adenylyl cyclase enhances desensitization of cyclic adenosine monophosphate signal and increases Akt signal with chronic catecholamine stress2007

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

      Circulation 116

      Pages: 1776-1783

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Disruption of type 5 adenylyl cyclase enhances desensitizationof cyclic adenosine monophosp hate signal and increases Akt signal with chronic catec holamine stress2007

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

      Circulation 116

      Pages: 1776-1783

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Drug therapy aimed at adenylyl cyclase to regulate cyclic nucleotide signaling2006

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

      Endocr Metab Immune Disord Drug Targets 5

      Pages: 239-247

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Drug therapy aimed at adenylyl cyclase to regulate cyclic nucleotide signaling2006

    • Author(s)
      Iwatsubo, K., et. al.
    • Journal Title

      Endocr Metab Immune Disord Drug Targets 5

      Pages: 239-247

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Genetic manipulation and functional analysis of cAMP signalling in cardiac muscle: implications for a new target of pharmacotherapy2005

    • Author(s)
      Ishikawa Y, Iwatsubo K, Tsunematsu T, Okumura S
    • Journal Title

      Biochem Soc Trans 33

      Pages: 1337-1340

    • Description
      「研究成果報告書概要(和文)」より
    • Peer Reviewed
  • [Journal Article] Genetic manipulation and functional analysis of cAMP signalling in cardiac muscle: implications for a new target of pharmacotherapy2005

    • Author(s)
      Ishikawa, Y., Iwatsubo, K., Tsunematsu, T., Okumura, S
    • Journal Title

      BiochemSocTrans 33

      Pages: 1337-1340

    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Type 5 adenylylcyclase plays a major role in regulating autonomic response for microgravity in the heart2008

    • Author(s)
      Bai Y, Okumura S, et. al.
    • Organizer
      第72回日本循環器学会学術集会
    • Place of Presentation
      福岡
    • Year and Date
      20080300
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Type 5 adenylylcyclase plays a major role in regulating autonomic response for microgravity in the heart2008

    • Author(s)
      Bai, Y., Okumura, S., et. al.
    • Organizer
      The 72nd Annual Scientific Meeting of the Japanese CirculationSociety
    • Place of Presentation
      Fukuoka, Japan
    • Year and Date
      20080300
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Disruption of type 5 adenylyl cyclase preserves cardiac function against chroniccatecholamine stress2007

    • Author(s)
      Okumura S, et. al.
    • Organizer
      第11回日本心不全学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Type 5 adenylyl cyclase hampers desensitization of cAMP signal in the heart2007

    • Author(s)
      Okumura S, et. al.
    • Organizer
      第11回日本心不全学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Disruption of type 5 adenylyl cyclase preserves cardiac function against chronic catecholamine stress2007

    • Author(s)
      Okumura, S., et. al.
    • Organizer
      The 11th Japanese Heart FailureSociety
    • Place of Presentation
      Tokyo,Japan
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Type 5 adenylyl cyclase hampers desensitization of cAMP signal in the heart2007

    • Author(s)
      Okumura, S., et. al.
    • Organizer
      The llth Japanese Heart Failure Society
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      20070900
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Type 5 Adenylyl Cyclase Hampers Desensitization of cAMP Signal to Attenu Akt Signal and Myocyte Viability in the Heart2006

    • Author(s)
      Okumura S, et. al.
    • Organizer
      第70回日本循環器学会学術集会
    • Place of Presentation
      名古屋
    • Year and Date
      20060400
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Type 5 Adenylyl Cyclase Hampers Desensitization of cAMP Signal to Attenuate Akt Signal and Myocyte Viability in the Hear2006

    • Author(s)
      Okumura, S., et. al.
    • Organizer
      The 70th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Nagoya, Japan
    • Year and Date
      20060400
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Disruption of type 5 adenylyl cyclase enhances desensitization of the cAMP signal and increases the Akt signal following chronic catecholamine stress2005

    • Author(s)
      Okumura S, et. al.
    • Organizer
      American Heart Association Scientific Sessions 2005
    • Place of Presentation
      Dallas in USA
    • Year and Date
      20051100
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Disruption of type 5 adenylyl cyclase enhances desensitization of the cAMP signal and increases the Akt signal following chronic catecholamine stress2005

    • Author(s)
      Okumura, S., et. al.
    • Organizer
      American Heart Association Scientific Sessions 2005
    • Place of Presentation
      Dallas, USA
    • Year and Date
      20051100
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] Effects of Chronic Beta-Adrenergic Receptor Stimulation in Type 5 Adenylyl Cyclase-Null Mice2005

    • Author(s)
      Effects of Chronic Beta-Adrenergic Cyclase-Null Mice
    • Organizer
      第69回日本循環器学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      20050400
    • Description
      「研究成果報告書概要(和文)」より
  • [Presentation] Effects of Chronic Beta-Adrenergic Receptor Stimulation in Type 5 Adenylyl Cyclase-Null Mice2005

    • Author(s)
      Okumura, S., et. al.
    • Organizer
      The 69th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      Yokohama, Japan
    • Year and Date
      20050400
    • Description
      「研究成果報告書概要(欧文)」より
  • [Presentation] 成人期の心臓に特異的発現を示す5型アデニル酸シクラーゼの心不全発症に果す役割とその特異的抑制薬による新しい心不全治療2005

    • Author(s)
      奥村 敏, 他
    • Organizer
      日本心臓病学会学術集会 パネルディスカッション「心不全進展のメカニズムを考慮した分子レベルからの新たな心不全治療戦略」
    • Place of Presentation
      大阪
    • Year and Date
      20050000
    • Description
      「研究成果報告書概要(和文)」より

URL: 

Published: 2010-02-04  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi