Molecular and Cellular Biochemistry

, Volume 377, Issue 1–2, pp 35–44 | Cite as

TAK1 activates AMPK-dependent cell death pathway in hydrogen peroxide-treated cardiomyocytes, inhibited by heat shock protein-70

  • Zhiyu Chen
  • Xiaolu Shen
  • Fengyan Shen
  • Wei Zhong
  • Hai Wu
  • Sha Liu
  • Jiang Lai
Article
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Abstract

The aim of this current study is to investigate the potential role of AMP-activated protein kinase (AMPK) in hydrogen peroxide (H2O2)-induced cardiomyocyte death, and focused on the signaling mechanisms of AMPK activation by H2O2. We observed a significant AMPK activation in H2O2-treated cardiomyocytes (both primary cells and H9c2 line). Inhibition of AMPK by its inhibitor or RNAi-reduced H2O2-induced cardiomyocyte death. We here proposed that transforming growth factor-β-activating kinase 1 (TAK1) might be the upstream kinase for AMPK activation by H2O2. H2O2-induced TAK1 activation, which recruited and activated AMPK. TAK1 inhibitor significantly suppressed H2O2-induced AMPK activation and following cardiomyocyte death, while over-expression of TAK1-facilitated AMPK activation and aggregated cardiomyocyte death. Importantly, heat shock protein-70 (HSP-70)-reduced H2O2-induced reactive oxygen species (ROS) accumulation, the TAK1/AMPK activation and cardiomyocyte death. In conclusion, we here suggest that TAK1 activates AMPK-dependent cell death pathway in H2O2-treated cardiomyocytes, and HSP-70 inhibits the signaling pathway by reducing ROS content.

Keywords

H2O2 ROS AMPK TAK1 HSP-70 and cardiomyocyte death 

Abbreviations

TAK1

Transforming growth factor-β-activating kinase 1

AMPK

AMP-activated protein kinase

HSP-70

Heat shock protein-70 m

H2O2

Hydrogen peroxide

MTT

3-[4,5-Dimethylthylthiazol-2-yl]-2,5 diphenyltetrazolium bromide

MAPK

Mitogen-activated protein kinase

IP

Immunoprecipitation

ROS

Reactive oxygen species

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Notes

Acknowledgments

This study was supported in part by the National Natural Science Foundation of China (Grant No: 81000787).

Conflict of interest

The authors have no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Zhiyu Chen
    • 1
  • Xiaolu Shen
    • 1
  • Fengyan Shen
    • 1
  • Wei Zhong
    • 1
  • Hai Wu
    • 1
  • Sha Liu
    • 1
  • Jiang Lai
    • 1
  1. 1.Division of Anesthesia and Critical Care MedicineXinhua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

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