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

Yang,Jia; Zhang,Yanmei; Zhao,Shigang; Zhang,Zhelin; Tong,Xiuqing; Wei,Fang; Lu,Zuneng

doi:10.3892/mmr.2015.4027

October-2015 Volume 12 Issue 4

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October-2015 Volume 12 Issue 4

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Article

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

Authors:
- Jia Yang
- Yanmei Zhang
- Shigang Zhao
- Zhelin Zhang
- Xiuqing Tong
- Fang Wei
- Zuneng Lu
View Affiliations / Copyright

Affiliations: Department of Neurology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China, Department of Neurology, The People's Hospital of Inner Mongolia, Hohhot, Inner Mongolia 010055, P.R. China, Department of Neurology, Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010059, P.R. China
Pages: 5524-5530
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Published online on: July 2, 2015

https://doi.org/10.3892/mmr.2015.4027
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Abstract

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.

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