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Exogenous HSP70 and Signaling Pathways Involved in the Inhibition of LPS-Induced Neurotoxicity of Neuroblastoma Cells

  • MOLECULAR CELL BIOLOGY
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Abstract

Neuroinflammation plays a key role in the pathogenesis of neurodegenerative diseases. Microglial cells are the main immune cells of the central nervous system. On exposure to lipopolysaccharides (LPS, components of the cell wall of Gram-negative enterobacteria), microglia is activated to produce reactive oxygen species (ROS), cytokines, and inflammatory mediators, which may cause neuron death. Exogenous recombinant human heat shock protein 70 (HSP70) was tested for effect on the activation of human microglial and neuroblastoma cells in response to LPS from Escherichia coli. Experiments included cell cultivation separately and transferring the conditioned medium from A-172 microglial cells to SK-N-SH neuroblastoma cells to simulate the effect of microglia treated with LPS and/or HSP70. The levels of ROS, TNFα, and apoptosis in LPS-treated cells were estimated in the presence or absence of HSP70. HSP70 was found to reduce the LPS-induced ROS generation, TNFα production, apoptosis, and necrosis, in both separate cell cultures and neuroblastoma cells grown in the conditioned medium from microglial cells. Signaling pathways involving protein kinases p38MAPK, JNK, and PI3K were demonstrated to play an important role in HSP70-mediated protection of microglial and neuroblastoma cells from LPS-induced apoptosis and ROS production.

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Funding

This work was supported by the Russian Foundation for Basic Research (project no. 19-04-00109). Isolation and purification of recombinant human HSP70 were supported by the Russian Science Foundation (project no. 19-14-00167) (D.G.).

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, 119991, Moscow, Russia

    M. M. Yurinskaya, D. G. Garbuz & M. B. Evgen’ev

  2. Institute of Cell Biophysics, Russian Academy of Sciences, 142290, Pushchino, Moscow region, Russia

    M. M. Yurinskaya, M. B. Evgen’ev & M. G. Vinokurov

Authors
  1. M. M. Yurinskaya
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  2. D. G. Garbuz
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  3. M. B. Evgen’ev
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  4. M. G. Vinokurov
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Correspondence to M. B. Evgen’ev.

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This article does not contain any studies involving animals or human subjects performed by any of the authors.

Conflict of interests. The authors declare that they have no conflict of interest.

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Translated by T. Tkacheva

Abbreviations: HSP70, heat shock protein, 70 kDa; LPS, lipopolysaccharide; ROS, reactive oxygen species.

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Yurinskaya, M.M., Garbuz, D.G., Evgen’ev, M.B. et al. Exogenous HSP70 and Signaling Pathways Involved in the Inhibition of LPS-Induced Neurotoxicity of Neuroblastoma Cells. Mol Biol 54, 111–118 (2020). https://doi.org/10.1134/S0026893320010161

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