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The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes

Author

Listed:
  • Sung-Young Shin

    (Korea Advanced Institute of Science and Technology (KAIST))

  • Taeyong Kim

    (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))

  • Ho-Sung Lee

    (Korea Advanced Institute of Science and Technology (KAIST)
    Graduate School of Medical Science and Engineering, KAIST)

  • Jun Hyuk Kang

    (Korea Advanced Institute of Science and Technology (KAIST)
    Graduate School of Medical Science and Engineering, KAIST)

  • Ji Young Lee

    (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))

  • Kwang-Hyun Cho

    (Korea Advanced Institute of Science and Technology (KAIST)
    Graduate School of Medical Science and Engineering, KAIST)

  • Do Han Kim

    (School of Life Sciences and Systems Biology Research Center, Gwangju Institute of Science and Technology (GIST))

Abstract

How cell fate (survival or death) is determined and whether such determination depends on the strength of stimulation has remained unclear. In this study, we discover that the cell fate of cardiomyocytes switches from survival to death with the increase of β-adrenergic receptor (β-AR) stimulation. Mathematical simulations combined with biochemical experimentation of β-AR signalling pathways show that the gradual increment of isoproterenol (a non-selective β1/β2-AR agonist) induces the switching response of Bcl-2 expression from the initial increase followed by a decrease below its basal level. The ERK1/2 and ICER-mediated feed-forward loop is the hidden design principle underlying such cell fate switching characteristics. Moreover, we find that β1-blocker treatment increases the survival effect of β-AR stimuli through the regulation of Bcl-2 expression leading to the resistance to cell death, providing new insight into the mechanism of therapeutic effects. Our systems analysis further suggests a novel potential therapeutic strategy for heart disease.

Suggested Citation

  • Sung-Young Shin & Taeyong Kim & Ho-Sung Lee & Jun Hyuk Kang & Ji Young Lee & Kwang-Hyun Cho & Do Han Kim, 2014. "The switching role of β-adrenergic receptor signalling in cell survival or death decision of cardiomyocytes," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6777
    DOI: 10.1038/ncomms6777
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    Cited by:

    1. Keun-Woo Lee & So-Young Yeo & Jeong-Ryeol Gong & Ok-Jae Koo & Insuk Sohn & Woo Yong Lee & Hee Cheol Kim & Seong Hyeon Yun & Yong Beom Cho & Mi-Ae Choi & Sugyun An & Juhee Kim & Chang Ohk Sung & Kwang-, 2022. "PRRX1 is a master transcription factor of stromal fibroblasts for myofibroblastic lineage progression," Nature Communications, Nature, vol. 13(1), pages 1-23, December.

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