Neuroprotective effect of dual specificity phosphatase 6 against glutamate-induced cytotoxicity in mouse hippocampal neurons

作者：Huang, Xiaoyun; Liao, Wang; Huang, Yihong; Jiang, Mujun; Chen, Jianjun; Wang, Mingxia; Lin, Han; Guan, Shaobing; Liu, Jun^*

来源：Biomedicine & Pharmacotherapy, 2017, 91: 385-392.

DOI：10.1016/j.biopha.2017.04.096

• dual specificity phosphatase 6
• glutamate
• hippocampal neurons
• neuroprotective effect
• ERK1/2

Dual specificity phosphatase 6 (DUSP6), a member of the dual specificity protein phosphatase subfamily, can inactivate ERK1/2. However, its possible role in glutamate-induced oxidative cytotoxicity effects is not clear. Here, we aimed to investigate whether DUSP6 was neuroprotective against glutamate-induced cytotoxicity in HT22 mouse hippocampal cells and primary cultured hippocampal neurons (pc-HNeu). HT22 and pc-HNeu cells were treated with varying concentrations of glutamate (from 0.05 mM to 5.0 mM) and DUSP6 protein expression were detected by western blotting. DUSP6-overexpressing HT22 and pc-HNeu cells were generated by transfection with DUSP6-overexpressing plasmid. The effects of DUSP6 overexpression on glutamate-induced cytotoxicity, cell death, cell apoptosis, and cell autophagy were determined by cell proliferation assays, flow cytometry, transmission electron microscopy, and western blotting. Glutamate treatment from 0.5 mM to 5.0 mM downregulated DUSP6 protein expression in both HT22 and pc-HNeu cells. DUSP6 overexpression ameliorated glutamate-induced cell death, apoptosis, and autophagy in both HT22 and pc-HNeu cells. Furthermore, ERK1/2 phosphorylation was decreased by DUSP6 overexpression. In conclusion, DUSP6 has neuroprotective effects against glutamate-induced cytotoxicity in HT22 and pc-HNeu cells. Targeting DUSP6 may be a useful strategy to prevent neuronal death in neurodegenerative diseases including AD.

• 出版日期2017-7
• 单位广东医科大学; 中山大学; 蚌埠医学院