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TDCPP protects cardiomyocytes from H2O2-induced injuries via activating PI3K/Akt/GSK3β signaling pathway

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Abstract

Tris (1, 3-dichloro-2-propyl) phosphate (TDCPP) is a major type of organophosphorus flame retardants, and long-term exposure to TDCPP to normal cells or tissues under physiological conditions can induce toxic effects. But how TDCPP leads to the adverse effects is not yet clear, and the effect of TDCPP under pathological conditions such as reactive oxygen species assault is not well understood. The present study aimed to explore the potential effect of TDCPP against H2O2-induced oxidative stress in H9c2 cardiomyoblasts and rat neonatal cardiomyocytes. We found that H2O2-treatment decreased cell viability and increased lactate dehydrogenase and malondialdehyde generation of H9c2 cells. However, TDCPP could alleviate these effects. TDCPP alleviated Ca2+-overload caused by H2O2 through decreasing store-operated calcium entry. More importantly, TDCPP remarkably decreased H2O2-induced dephosphorylation of Akt and GSK3β, and through this pathway TDCPP mitigated the H2O2-induced apoptosis and detrimental autophagy. Collectively, via mitigating Ca2+-overload and activating the Akt/GSK3β signaling pathway, TDCPP may have a role in protecting cardiomyocytes from oxidative stress.

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Acknowledgements

This research was supported by the National Natural Science Foundation of China Grants 30970662 (to Y.H.) and the Natural Science Foundation of Hubei Province of China 2018CFB668 (to X.J.).

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Authors and Affiliations

  1. Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei, China

    Weishan Zhang, Xin Hou, Mengjun Huang, Xixi Zeng & Yanhong Liao

  2. Department of Anatomy, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Xiju He

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  1. Weishan Zhang
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Correspondence to Xiju He or Yanhong Liao.

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Zhang, W., Hou, X., Huang, M. et al. TDCPP protects cardiomyocytes from H2O2-induced injuries via activating PI3K/Akt/GSK3β signaling pathway. Mol Cell Biochem 453, 53–64 (2019). https://doi.org/10.1007/s11010-018-3431-8

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