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

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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.

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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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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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Authors and Affiliations

  1. Division of Anesthesia and Critical Care Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 1665 Kong-jiang Road, Yangpu District, Shanghai, 200092, China

    Zhiyu Chen, Xiaolu Shen, Fengyan Shen, Wei Zhong, Hai Wu, Sha Liu & Jiang Lai

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  1. Zhiyu Chen
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  2. Xiaolu Shen
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  3. Fengyan Shen
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  4. Wei Zhong
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  5. Hai Wu
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  6. Sha Liu
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  7. Jiang Lai
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Correspondence to Jiang Lai.

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Chen Zhiyu and Shen Xiaolu contributed equally.

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Chen, Z., Shen, X., Shen, F. et al. TAK1 activates AMPK-dependent cell death pathway in hydrogen peroxide-treated cardiomyocytes, inhibited by heat shock protein-70. Mol Cell Biochem 377, 35–44 (2013). https://doi.org/10.1007/s11010-013-1568-z

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  • DOI: https://doi.org/10.1007/s11010-013-1568-z

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