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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This study was supported in part by the National Natural Science Foundation of China (Grant No: 81000787).
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The authors have no conflict of interest.
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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