title: TAK1 activates AMPK-dependent cell death pathway in hydrogen peroxide-treated cardiomyocytes, inhibited by heat shock protein-70.
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.
authors: Division of Anesthesia and Critical Care Medicine, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Yangpu District, Shanghai, China.
authors: Zhiyu
authors: Z
authors: Chen
authors: Xiaolu
authors: X
authors: Shen
authors: Fengyan
authors: F
authors: Shen
authors: Wei
authors: W
authors: Zhong
authors: Hai
authors: H
authors: Wu
authors: Sha
authors: S
authors: Liu
authors: Jiang
authors: J
authors: Lai
mesh_terms: D000263:Adenylate Kinase / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival; D004789:Enzyme Activation; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000502:physiology; D016877:Oxidants / Q000494:pharmacology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D012118:Resorcinols / Q000494:pharmacology; D015398:Signal Transduction; D000099151:MAP Kinase Kinase Kinase 7; D015025:Zearalenone / Q000008:administration & dosage
chemical_list: D000263:Adenylate Kinase; D018840:HSP70 Heat-Shock Proteins; D006861:Hydrogen Peroxide; D007783:Lactones; D020930:MAP Kinase Kinase Kinases; D016877:Oxidants; D017382:Reactive Oxygen Species; D012118:Resorcinols; D000099151:MAP Kinase Kinase Kinase 7; C505734:7-oxozeanol; D015025:Zearalenone
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