Glutamine promotes Hsp70 and inhibits α-Synuclein accumulation in pheochromocytoma PC12 cells

Wang,Haiyang; Tang,Chongyang; Jiang,Zhenfeng; Zhou,Xiao; Chen,Jianhang; Na,Meng; Shen,Hong; Lin,Zhiguo

doi:10.3892/etm.2017.4580

Glutamine promotes Hsp70 and inhibits α-Synuclein accumulation in pheochromocytoma PC12 cells

Authors:
- Haiyang Wang
- Chongyang Tang
- Zhenfeng Jiang
- Xiao Zhou
- Jianhang Chen
- Meng Na
- Hong Shen
- Zhiguo Lin
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Affiliations: Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
Published online on: June 12, 2017 https://doi.org/10.3892/etm.2017.4580
Pages: 1253-1259

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Abstract

Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln‑induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription- quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)‑1 was required for this phenomenon with an RNA interference strategy. The regulatory role of Gln on α‑Syn degeneration was also determined in the α‑Syn‑overexpressed PC12 [PC12 (α‑Syn+)] cells, which were treated with or without the proteasomal inhibitor lactacystin (Lac). The results demonstrated that treatment with ≥10 mM Gln significantly increased Hsp70 mRNA and protein levels (P<0.05) and that this promotion was HSF‑1‑dependent, as HSF‑1 knockout with HSF‑1‑specific small interfering RNA abrogated Hsp70 promotion in PC12 (α‑Syn+) cells. Furthermore, Gln treatment markedly upregulated α‑Syn degeneration in PC12 (α‑Syn+) cells, which was significantly reduced (P<0.05) in the presence of Lac. Therefore, the present study suggests that Gln is able to induce the promotion of Hsp70 expression in PC12 cells in an HSF‑1‑dependent manner and that Gln‑mediated Hsp70 promotion may increase α‑Syn degradation even in the presence of proteasomal inhibitor. Thus, glutamine may be a potential therapeutic agent to prevent α‑Syn aggregation in PD.

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