The Role of p53 Protein in the Realization of the Exogenous Heat Shock Protein 70 Anti-Apoptotic Effect during Axotomy

Cells. 2021 Dec 29;11(1):93. doi: 10.3390/cells11010093.

Abstract

The search for effective neuroprotective agents for the treatment of neurotrauma has always been of great interest to researchers around the world. Extracellular heat shock protein 70 (eHsp70) is considered a promising agent to study, as it has been demonstrated to exert a significant neuroprotective activity against various neurodegenerative diseases. We showed that eHsp70 can penetrate neurons and glial cells when added to the incubation medium, and can accumulate in the nuclei of neurons and satellite glial cells after axotomy. eHsp70 reduces apoptosis and necrosis of the glial cells, but not the neurons. At the same time, co-localization of eHsp70 with p53 protein, one of the key regulators of apoptosis, was noted. eHsp70 reduces the level of the p53 protein apoptosis promoter both in glial cells and in the nuclei and cytoplasm of neurons, which indicates its neuroprotective effect. The ability of eHsp70 to reverse the proapoptotic effect of the p53 activator WR1065 may indicate its ability to regulate p53 activity or its proteosome-dependent degradation.

Keywords: axotomy; exogenous Hsp70; neurotrauma; p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis*
  • Astacoidea / metabolism*
  • Axotomy*
  • Down-Regulation
  • E2F1 Transcription Factor / metabolism
  • HSP70 Heat-Shock Proteins / isolation & purification
  • HSP70 Heat-Shock Proteins / metabolism*
  • Humans
  • Mechanoreceptors / metabolism
  • Mercaptoethylamines / pharmacology
  • Necrosis
  • Neuroglia / metabolism
  • Neurons / metabolism
  • Proto-Oncogene Proteins c-myc / metabolism
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • E2F1 Transcription Factor
  • HSP70 Heat-Shock Proteins
  • Mercaptoethylamines
  • Proto-Oncogene Proteins c-myc
  • Recombinant Proteins
  • Tumor Suppressor Protein p53
  • N-(2-mercaptoethyl)-1,3-diaminopropane