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Oxidative stress during fetal-neonatal transition and the formation of a positive-feedback loop for the terminal differentiation of mammalian cardiomyocytes.

Research Project

Project/Area Number 22300148
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionHokkaido University

Principal Investigator

KAWAHARA Koichi  北海道大学, 名誉教授 (20125397)

Co-Investigator(Kenkyū-buntansha) SAITOH Tadashi  山形大学, 大学院・理工学研究科, 助教 (20454770)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥17,680,000 (Direct Cost: ¥13,600,000、Indirect Cost: ¥4,080,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2010: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
Keywords心筋細胞 / 細胞周期 / 酸化ストレス / 正帰還ループ / 増殖能喪失
Research Abstract

Shortly after birth, mammalian cardiomyocytes irreversibly exit from the cell cycle and become terminally differentiated. The genetic cues for the irreversible exit from the cell cycle in mammalian cardiomyocytes soon after birth remain largely unknown. We examined whether and if so how oxidative stress to mammalian hearts during fetal-neonatal transition produces changes in the proliferative activity and terminal differentiation of cardiomyocytes. Scavenging of reactive oxygen species (ROS) during fetal-neonatal transition, especially after birth, resulted in an increase in the proliferative activity and a decrease in the ratio of binucleated cardiomyocytes. Exposure to ROS in cultured cardiomyocytes increased the activity of p38 MAPK and the expression of connexin43 (Cx43). Not only knockdown of Cx43 using siRNA but also the inhibition of p38 MAPK activity resulted in a significant decrease in the production of ROS in cardiomyocytes. This study demonstrated that the ROS-induced formation of a positive-feedback loop ROS-p38 MAPK-mtCx43 for the sustained activation of p38 MAPK soon after birth possibly contributes to the loss of cell division and binucleation in mammalian cardiomyocytes.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report
  • Research Products

    (23 results)

All 2013 2012 2011 2010 Other

All Journal Article (12 results) (of which Peer Reviewed: 10 results) Presentation (6 results) Book (1 results) Remarks (4 results)

  • [Journal Article] Spatio-temporal spread of neuronal death after focal photolysis of caged glutamate in neuron/astrocyte co-cultures.2013

    • Author(s)
      Sadahiro Iwabuchi
    • Journal Title

      Neurochemistry International

      Volume: 62 Issue: 7 Pages: 1020-1027

    • DOI

      10.1016/j.neuint.2013.03.010

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Direct observation of dynamic force propagation between focal adhesions of cells on microposts by atomic force microscopy2011

    • Author(s)
      A.Okada, 他6名, T.Okajima
    • Journal Title

      Appl.Phys.Lett.

      Volume: 99 Issue: 26 Pages: 263703-263703

    • DOI

      10.1063/1.3672225

    • NAID

      120003783352

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Negative-feedback regulation of ATP release : ATP release from cardiomyocytes is strictly regulated during ischemia2011

    • Author(s)
      Kunugi, 他2名, Okajima, T., Kawahara, K.
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 416 Issue: 3-4 Pages: 409-415

    • DOI

      10.1016/j.bbrc.2011.11.068

    • NAID

      120003762601

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Rheological Properties of Growth-Arrested Fibroblast Cells under Serum Starvation Measured by Atomic Force Microscopy2011

    • Author(s)
      A.Miyaoka, 他3名, T.Okajima
    • Journal Title

      Jpn.J.Appl.Phys.

      Volume: 50 Issue: 8S3 Pages: 08LB16-08LB16

    • DOI

      10.1143/jjap.50.08lb16

    • NAID

      210000071145

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inducible astrocytic glucose transporter-3 contributes to the enhanced storage of intracellular glycogen during reperfusion after ischemia2011

    • Author(s)
      Iwabuchi, S. and Kawahara, K.
    • Journal Title

      Neurochemistry International

      Volume: 59 Issue: 2 Pages: 319-325

    • DOI

      10.1016/j.neuint.2011.06.006

    • NAID

      120003340662

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Oxidativestress-induced formation of a positive-feedback loop for the sustained activation of p38 MAPK leading to the loss of cell division in cardiomyocytes soon after birth2011

    • Author(s)
      Matsuyama, D. and Kawahara, K.
    • Journal Title

      Basic Research in Cardiology

      Volume: 106 Issue: 5 Pages: 815-828

    • DOI

      10.1007/s00395-011-0178-8

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 10 Hz periodic component influences lower frequency component of the physiological tremor at low force levels2011

    • Author(s)
      Endo, H. and Kawahara, K.
    • Journal Title

      European Journal of Applied Physiology

      Volume: 111 Issue: 11 Pages: 2695-2705

    • DOI

      10.1007/s00421-011-1903-6

    • NAID

      120004856988

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Functional significance of the negative-feedback regulation of ATP release via pannexin-1 hemichannels under ischemic stress in astrocytes2011

    • Author(s)
      Iwabuchi, S. and Kawahara, K.
    • Journal Title

      Neurochemistry International

      Volume: 58 Issue: 3 Pages: 376-384

    • DOI

      10.1016/j.neuint.2010.12.013

    • NAID

      120003464638

    • Related Report
      2012 Final Research Report 2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gender differences in hand stability assessed in normal young people2011

    • Author(s)
      Endo, H. and Kawahara, K.
    • Journal Title

      Ergonomics

      Volume: 54(3) Pages: 273-281

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Relationship between hand stability and the 10-Hz physiological tremor during various manual tasks2010

    • Author(s)
      Endo, H. and Kawahara, K.
    • Journal Title

      Ergonomics

      Volume: 53(4) Issue: 4 Pages: 491-501

    • DOI

      10.1080/00140130903556336

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] 成ラット単離心筋細胞の高頻度電気刺激による細胞内Ca^<2+>およびMg^<2+>のダイナミクス2010

    • Author(s)
      五十嵐博之, 他
    • Journal Title

      電子情報通信学会技術研究報告

      Volume: MBE-123 Pages: 123-125

    • Related Report
      2010 Annual Research Report
  • [Journal Article] ケージドグルタミン酸への局所的な光照射を用いたin vitro新規脳虚血モデルの開発2010

    • Author(s)
      渡辺知晴, 他
    • Journal Title

      電子情報通信学会技術研究報告

      Volume: MBE-123 Pages: 23-26

    • Related Report
      2010 Annual Research Report
  • [Presentation] Negative-feedback regulation of ATP release during ischemia in cardiac myocytes.2012

    • Author(s)
      Koichi Kawahara
    • Organizer
      World Congress on Medical Physics & Biomedical Engineering
    • Place of Presentation
      Beijing International Congress Center (中国)
    • Related Report
      2012 Annual Research Report
  • [Presentation] Positive-feedback regulation loop for the loss of cell division and binucleation shortly after birth in cardiomyocytes2011

    • Author(s)
      Kawahara, K., Matsuyama, D.
    • Organizer
      5^<th> European Congress of IFMBE
    • Place of Presentation
      Budapest Congress & World Trade Center (Hungary)
    • Year and Date
      2011-09-15
    • Related Report
      2011 Annual Research Report
  • [Presentation] 虚血時における心筋細胞のATP放出制御とそのシグナル伝達機構に関する研究2011

    • Author(s)
      功刀聡彦,岩淵禎弘,松山大輔,河原剛一
    • Organizer
      MEとバイオサイバネティクス研究会
    • Place of Presentation
      東京,玉川大学
    • Related Report
      2012 Final Research Report
  • [Presentation] 原子間力顕微鏡を用いた正常・老化・不死化細胞の力学統計解析2010

    • Author(s)
      水谷祐輔, 他
    • Organizer
      第49回日本生体医工学会北海道支部大会
    • Place of Presentation
      北海道大学(札幌)
    • Year and Date
      2010-10-09
    • Related Report
      2010 Annual Research Report
  • [Presentation] ケージ ドグルタミン酸への局所的な光照射を用いたin vitro新規脳虚血モデルの開発2010

    • Author(s)
      渡辺知晴,岩淵禎弘,河原剛一
    • Organizer
      MEとバイオサイバネティクス研究会
    • Place of Presentation
      札幌,北海道大学
    • Related Report
      2012 Final Research Report
  • [Presentation] 成ラット単離心筋細胞の高頻度電気刺激による細胞内Ca2+およびMg2+のダイナミクス2010

    • Author(s)
      五十嵐博之,水谷祐輔,岩淵禎弘,松山大輔,河原剛一
    • Organizer
      MEとバイオサイバネティクス研究会
    • Place of Presentation
      東京,玉川大学
    • Related Report
      2012 Final Research Report
  • [Book] In: Proceedings ofthe IFMBE 37, Jobbagy, A. (Ed.), Springer-Verlag, Berlin2011

    • Author(s)
      Kawahara, K. and Matsuyama, D.
    • Publisher
      Positive-feedback regulation loop for the loss of cell division and binucleation shortly after birth in cardiomyocytes
    • Related Report
      2012 Final Research Report
  • [Remarks]

    • URL

      http://cell-c.ist.hokudai.ac.jp

    • Related Report
      2012 Final Research Report
  • [Remarks] 北海道大学・大学院情報科学研究科・細胞情報工学研究室

    • URL

      http://cell-c.ist.hokudai.ac.jp

    • Related Report
      2012 Annual Research Report
  • [Remarks]

    • URL

      http://cell-c.ist.hokudai.ac.jp

    • Related Report
      2011 Annual Research Report
  • [Remarks]

    • URL

      http://cell-c.ist.hokudai.ac.jp

    • Related Report
      2010 Annual Research Report

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Published: 2010-08-23   Modified: 2019-07-29  

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