Heat shock protein 70 induction by glutamine increases the α-synuclein degradation in SH-SY5Y neuroblastoma cells

Mol Med Rep. 2015 Oct;12(4):5524-30. doi: 10.3892/mmr.2015.4027. Epub 2015 Jul 2.


Functional defects in heat shock proteins (HSPs), e.g. Hsp70, have been reported to have a key role in Parkinson's disease (PD). Overexpressed Hsp70 re‑folds aggregated α‑synuclein to generate the non‑toxic and non‑aggregated form. Thus, Hsp70 is a well‑defined therapeutic target, and Hsp70 promotion is an efficient strategy to prevent or even reverse the α‑synuclein‑induced toxicity in PD. The present study investigated the promotion of Hsp70 expression in SH‑SY5Y neuroblastoma cells by glutamine (Gln), which has recently been recognized to induce Hsp70 expression. Furthermore, the role of heat shock factor (HSF)‑1 in the Gln‑mediated upregulation of Hsp70 expression was investigated. In addition, the regulatory role of Gln in α‑synuclein degradation in α‑synuclein‑overexpressing SH‑SY5Y cells was determined. The results of the present study demonstrated that Gln treatment significantly upregulated Hsp70 expression at the mRNA as well as the protein level in a dose‑dependent and time‑dependent manner. Gln‑induced Hsp70 upregulation was found to be HSF‑1‑dependent, as HSF‑1 knockdown abrogated the Hsp70 upregulation by Gln in α‑synuclein‑overexpressing SH‑SY5Y cells. In conclusion, present study confirmed that Gln upregulates Hsp70 expression in SH‑SY5Y neuroblastoma cells in an HSF‑1‑dependent manner. The upregulation of Hsp70 by Gln increases the α‑synuclein degradation. Therefore, Gln may be a potential therapeutic agent to prevent α‑synuclein aggregation in PD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / drug effects
  • Glutamine / metabolism*
  • Glutamine / pharmacology
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Heat Shock Transcription Factors
  • Humans
  • Neuroblastoma / metabolism*
  • Proteolysis
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Up-Regulation
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*


  • DNA-Binding Proteins
  • HSF1 protein, human
  • HSP70 Heat-Shock Proteins
  • Heat Shock Transcription Factors
  • Transcription Factors
  • alpha-Synuclein
  • Glutamine