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Regulation of L-type calcium channel by intracellular subunit in cardiac hypertrophy and failure.

Research Project

Project/Area Number 23390212
Research Category

Grant-in-Aid for Scientific Research (B)

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

Principal Investigator

NAKAYAMA HIROYUKI  大阪大学, 薬学研究科(研究院), 准教授 (40581062)

Co-Investigator(Kenkyū-buntansha) ASAHI Michio  大阪医科大学, 薬理学, 教授 (10397614)
FUJIO Yasushi  大阪大学, 薬学研究科, 教授 (20359839)
Project Period (FY) 2011-04-01 – 2014-03-31
Project Status Completed (Fiscal Year 2013)
Budget Amount *help
¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000)
Fiscal Year 2013: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Keywordsカルシウム / チャネル / 心肥大 / 心不全 / カルモデュリン依存性キナーゼ / マイクロドメイン / シグナリング / カルシウムチャネル / プロテインキナーゼA / 細胞死
Research Abstract

L-type calcium channel (LTCC) localizes at T-tubules and caveolae in cardiomyocytes, and plays major roles in excitation-contraction coupling and cardiac hypertrophy. The expression of b2a subunit of LTCC (b2a) is increased in human failing heart. Phosphorylation of b2a by CaMKII enhanced LTCC activity. In the present study, we examined the pathological role of b2a phosphorylation in cardiac hypertrophy. We developed a method to examine caveolae-specific activation of CaMKII and found that b2a phosphorylation occurs specifically in caveolae and elicit myocyte hypertrophy in a1 adrenergic stimulation. Thus, we generated transgenic mice (TG) overexpressing non phosphorylated mutant of b2a.The expressions of b2a in both mutant and wild-type TG were similar. a1 adrenergic stimulation induced cardiac hypertrophy was attenuated in mutant TG compared to wild-type TG mice. In conclusion, we revealed that phosphorylated b2a localized at caveolae and exaggerates cardiac hypertrophy.

Report

(4 results)
  • 2013 Annual Research Report   Final Research Report ( PDF )
  • 2012 Annual Research Report
  • 2011 Annual Research Report
  • Research Products

    (30 results)

All 2014 2013 2012 2011 Other

All Journal Article (13 results) (of which Peer Reviewed: 5 results,  Open Access: 2 results) Presentation (15 results) (of which Invited: 2 results) Book (2 results)

  • [Journal Article] Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA22014

    • Author(s)
      Shintani Y, Drexler HC, Kioka H, Terracciano CM, Coppen SR, Imamura H, Akao M, Nakai J, Wheeler AP, Higo S, Nakayama H, 他3名
    • Journal Title

      EMBO Rep

      Volume: 15(4) Pages: 438-45

    • Related Report
      2013 Final Research Report
  • [Journal Article] Genetic modulation of the SERCA activity does not affect the Ca2+ leak from the cardiac sarcoplasmic reticulum2014

    • Author(s)
      Morimoto S, Hongo K, Kusakari Y, Komukai K, Kawai M, O-Uchi J, Nakayama H, 他4名
    • Journal Title

      Cell Calcium

      Volume: 55(1) Pages: 17-23

    • Related Report
      2013 Final Research Report
  • [Journal Article] Genetic modulation of the SERCA activity does not affect the Ca2+ leak from the cardiac sarcoplasmic reticulum.2014

    • Author(s)
      Morimoto S, Hongo K, Kusakari Y, Komukai K, Kawai M, O-Uchi J, Nakayama H, Asahi M, Otsu K, Yoshimura M, Kurihara S.
    • Journal Title

      Cell Calcium.

      Volume: 55 Issue: 1 Pages: 17-23

    • DOI

      10.1016/j.ceca.2013.10.005

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Toll-like receptor 9 protects non-immune cells from stress by modulating mitochondrial ATP synthesis through the inhibition of SERCA2.2014

    • Author(s)
      Shintani Y, Drexler HC, Kioka H, Terracciano CM, Coppen SR, Imamura H, Akao M, Nakai J, Wheeler AP, Higo S, Nakayama H, Takashima S, Yashiro K, Suzuki K.
    • Journal Title

      EMBO Reports

      Volume: 15 Issue: 4 Pages: 438-445

    • DOI

      10.1002/embr.201337945

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Calcium dependent signaling in cardiac hypertrophy and cell death2013

    • Author(s)
      Nakayama H, Fujio Y, Yamaguchi O
    • Journal Title

      Clin Calcium

      Volume: 23(4) Pages: 505-15

    • Related Report
      2013 Final Research Report
  • [Journal Article] Ras Homologue Enriched in Brain (Rheb) -dependent mTORC1 Activation Becomes Indispensable for Cardiac Hypertrophic Growth after Early Postnatal Period2013

    • Author(s)
      Tamai T, Yamaguchi O, Hikoso S, Takeda T, Taneike M, Oka T, Oyabu J, Murakawa T, Nakayama H, 他6名
    • Journal Title

      J Biol Chem

      Volume: 288(5) Pages: 10176-87

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cathelicidin antimicrobial peptide inhibits fibroblast migration via P2X7 receptor signaling.2013

    • Author(s)
      Kumagai, S., Matsui, K., Kawaguchi, H., Yamashita, T., Mohri, T., Fujio, Y., Nakayama, H.
    • Journal Title

      Biochem. Biophys. Res. Commun.

      Volume: 437 Issue: 4 Pages: 609-614

    • DOI

      10.1016/j.bbrc.2013.07.010

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy-mediated degradation is necessary for regression of cardiac hypertrophy during ventricular unloading.2013

    • Author(s)
      Oyabu J, Yamaguchi O, Hikoso S, Takeda T, Oka T, Murakawa T, Yasui H, Ueda H, Nakayama H, Taneike M, Omiya S, Shah AM, Nishida K, Otsu K.
    • Journal Title

      Biochemical and Biophysical Research Communication

      Volume: 441 Issue: 4 Pages: 787-792

    • DOI

      10.1016/j.bbrc.2013.10.135

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Ca2+依存性の心肥大・心筋細胞死誘導シグナル2013

    • Author(s)
      中山博之、山口修、藤尾慈
    • Journal Title

      Clinical Calcium

      Volume: 23 Pages: 505-515

    • Related Report
      2013 Annual Research Report
  • [Journal Article] Calcium influx through Cav1.2 is a proximal signal for pathological cardiomyocyte hypertrophy.2011

    • Author(s)
      Chen X
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 50 Issue: 3 Pages: 460-470

    • DOI

      10.1016/j.yjmcc.2010.11.012

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Autophagy-mediated degradation is necessary for regression of cardi ac hypertrophy during ventricular unloading

    • Author(s)
      Oyabu J, Yamaguchi O, Hikoso S, Takeda T, Oka T, Murakawa T, Yasui H, Ueda H, Nakayama H, 他5名
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 441(4) Pages: 787-92

    • Related Report
      2013 Final Research Report
  • [Journal Article] Cathelicidin antimicrobial peptide inhibits fibroblast migration via P2X7 receptor signaling

    • Author(s)
      Kumagai S, Matsui K, Kawaguchi H, Yamashita T, Mohri T, Fujio Y, Nakayama H
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 437(4) Pages: 609-14

    • Related Report
      2013 Final Research Report
  • [Journal Article] Requirement of SLD5 for early embryo-genesis

    • Author(s)
      Mohri T, Ueno M, Nagahama Y, Gong ZY, Asano M, Oshima H, Oshima M, Fujio Y, Takakura N
    • Journal Title

      PLoS One

      Volume: 8(11)

    • Related Report
      2013 Final Research Report
  • [Presentation] Caveolae- specific phosphorylation of L-type calcium channel b2a subunit exaggerates cardiac hypertrophic responses after a1 adrenergic stimulation in mice2014

    • Author(s)
      Hiroyuki Nakayama
    • Organizer
      American Heart Association
    • Place of Presentation
      Las Vegas
    • Related Report
      2013 Final Research Report
  • [Presentation] Phosphorylation of L-type Ca2+ channel b2a subunit induce cardiomyocyte hypertrophy2014

    • Author(s)
      早水菜緒
    • Organizer
      第87回日本薬理学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] Excessive BIN1 expression results in adverse remodeling through cardiomyocyte death2014

    • Author(s)
      舎川洸太
    • Organizer
      第87回日本薬理学会
    • Place of Presentation
      仙台
    • Related Report
      2013 Final Research Report
  • [Presentation] Excessive BIN1 expression results in adeverse remodeling through cardiomyocyte death2014

    • Author(s)
      Kota Tonegawa, Sachi Matsunami, Daisuke Tsuchiyama, Hiroyuki Nakayama, Yasushi Fujio
    • Organizer
      日本薬理学会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Phosphorylation of L-type Ca2+ channel b2a subunit induces cardiomyocyte hypertrophy2014

    • Author(s)
      Nao Hyamizu, Shohei Kumagai, Sachi Matsunami, Hiroyuki Nakayama, Yasushi Fujio
    • Organizer
      日本薬理学会
    • Place of Presentation
      仙台国際センター(仙台)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Caveolae-specific phosphorylation of L-type calcium channel 2a subunit exaggerates cardiac hypertrophic responses after 1 adrenergic stimulation in mice.2014

    • Author(s)
      Hiroyuki Nakayama, Shohei Kumagai, Sachi Matsunami, Nao Hayamizu Wataru Otsuka and Yasushi Fujio.
    • Organizer
      Basic Cardiovascular Sciences/American Heart Association
    • Place of Presentation
      Paris Las Vegas (ラスベガス)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Inhibition of P2X7 Receptor Signaling Promote Adverse Cardiac Remodeling after Myocardial Infarction thorough Enhanced Cardiac Fibroblast Migration2013

    • Author(s)
      Shohei Kumagai
    • Organizer
      American Heart Association
    • Place of Presentation
      Dallas
    • Related Report
      2013 Final Research Report
  • [Presentation] Inhibition of P2X7 Receptor Signaling Promote Adverse Cardiac Remodeling after Myocardial Infarction thorough Enhanced Cardiac Fibroblast Migration2013

    • Author(s)
      熊谷渉平
    • Organizer
      第21回血管生物学会
    • Place of Presentation
      大阪
    • Related Report
      2013 Final Research Report
  • [Presentation] Inhibition of P2X7 receptor signaling promotes adverse cardiac remodeling after myocardial infarction through enhanced cardiac fibroblast migration2013

    • Author(s)
      熊谷渉平 中山博之 宮脇昭光 毛利友美 藤尾慈
    • Organizer
      日本血管生物医学会
    • Place of Presentation
      千里国際阪急ホテル(大阪)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Inhibition of P2X7 Receptor Signaling Promotes Adverse Cardiac Remodeling after Myocardial Infarction through Enhanced Cardiac Fibroblast Migration2013

    • Author(s)
      Kumagai Shohei, Nakayama Hiroyuki, Miyawaki Akimitsu, Mohri Tomomi, Fujio Yasushi,
    • Organizer
      American Heart Association
    • Place of Presentation
      ダラス
    • Related Report
      2013 Annual Research Report
  • [Presentation] The myocardial activation of CaMKIIb leads to heart failure2013

    • Author(s)
      輪島こまゆ
    • Organizer
      第86回 日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Development of a novel tool for analysis of PKA and CaMKII activities in caveolae2013

    • Author(s)
      松浪佐知
    • Organizer
      第86回 日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] Cathelicidin antimicrobial peptide inhibits fibroblasts migration via P2X7 receptor signaling2013

    • Author(s)
      熊谷渉平
    • Organizer
      第86回 日本薬理学会年会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
  • [Presentation] オートファジーを免れたミトコンドリアDNAの蓄積は心臓において炎症と心不全を惹起する2012

    • Author(s)
      中山博之
    • Organizer
      第85回 日本生化学会大会
    • Place of Presentation
      福岡
    • Related Report
      2012 Annual Research Report
    • Invited
  • [Presentation] Calcium-mediated pathogenesis in heart2012

    • Author(s)
      中山 博之
    • Organizer
      日本薬理学会年回
    • Place of Presentation
      京都
    • Related Report
      2011 Annual Research Report
    • Invited
  • [Book] 遺伝子医学MOOK別冊 細胞死研究の今 –疾患との関わり、創薬に向けてのアプローチ−2013

    • Author(s)
      中山博之、大津欣也
    • Total Pages
      6
    • Publisher
      メディカルドゥ
    • Related Report
      2013 Annual Research Report
  • [Book] 遺伝子医学MOOK別冊細胞死研究の今

    • Author(s)
      中山博之, 他
    • Publisher
      メディカルドウ
    • Related Report
      2013 Final Research Report

URL: 

Published: 2011-04-06   Modified: 2019-07-29  

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