Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway

Xufang DAI; Xiaojing YAN; Peng XIE; Jiqin LIAN

doi:10.16016/j.1000-5404.202001055

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Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway

Neurosciences | 更新时间：2026-01-09

- Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway
- Journal of Third Military Medical University Vol. 42, Issue 12, Pages: 1195-1200(2020)
- 作者机构：
  
  1.400047 重庆，重庆师范大学：教育科学学院特殊教育系
  2.400047 重庆，重庆师范大学：重庆市特殊儿童心理诊断与教育技术重点实验室
  3.400038 重庆，陆军军医大学(第三军医大学)基础医学院生物化学与分子生物学教研室
- 作者简介：
- 基金信息：
  
  the National Natural Science Foundation for Young Scholars of China(31201068)
- DOI：10.16016/j.1000-5404.202001055
  CLC： R322.81; R965; R971.6
- Received：08 January 2020，
  
  Revised：2020-03-04，
  
  Published：30 June 2020
- 稿件说明：
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Xufang DAI, Xiaojing YAN, Peng XIE, et al. Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway[J]. Journal of Third Military Medical University, 2020, 42(12): 1195-1200.
DOI：

Xufang DAI, Xiaojing YAN, Peng XIE, et al. Sodium valproate promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway[J]. Journal of Third Military Medical University, 2020, 42(12): 1195-1200. DOI： 10.16016/j.1000-5404.202001055.

摘要

目的

探讨抗癫痫药丙戊酸钠(sodium valproate，VPA)对神经细胞的凋亡诱导作用及相关机制。

方法

将人神经母细胞瘤细胞(SH-SY5Y)用不同剂量VPA处理，流式分析细胞凋亡水平变化，Western blot检测Mcl-1蛋白水平变化，定量PCR分析Mcl-1 mRNA与miR-148a-3p水平变化，报告基因实验检测Mcl-1启动子活性变化。用miR-148a-3p抑制剂联合VPA处理细胞，观察miR-184a-3p在VPA下调Mcl-1表达中的作用及对VPA促SH-SY5Y细胞凋亡效果的影响。

结果

VPA可促进SH-SY5Y细胞凋亡，并抑制SH-SY5Y细胞中Mcl-1的蛋白和mRNA水平(

0.05)。VPA处理不影响SH-SY5Y细胞中Mcl-1的启动子活性(

0.05)。VPA可显著增强SH-SY5Y细胞中miR-148a-3p的表达(

0.05)，使用miR-148a-3p抑制剂可减轻VPA对Mcl-1表达的抑制作用，并减弱VPA的促细胞凋亡效果。

结论

VPA可能通过激活miR-148a-3p/Mcl-1信号通路促进SH-SY5Y细胞凋亡。

Abstract

Objective

To investigate the apoptosis-inducing effect of sodium valproate (VPA) on nerve cells and the underlying mechanism.

Methods

Human neuroblastoma SH-SY5Y cells treated with VPA of difterent doses were examined for apoptosis and Mcl-1 protein expression using flow cytometry and Western blotting

respectively. The mRNA expression of Mcl-1 and miR-148a-3p in the treated cells was detected with qRT-PCR

and the promoter activity of Mcl-1 gene was analyzed using a reporter gene assay. The changes of cell apoptosis and Mcl-1 expression in SH-SY5Y cells were analyzed following combined treatment with VPA and a miR-148a-3p antagonist.

Results

VPA treatment significantly promoted apoptosis and down-regulated Mcl-1 expression at both the mRNA and protein levels in SH-SY5Y cells. VPA treatment did not significantly affect the transcriptional activity of Mcl-1 promoter but up-regulated the expression of miR-148a-3p in SH-SY5Y cells. The application of the miR-148a-3p antagonist obviously attenuated the inhibitory effect of VPA on Mcl-1 expression and VPA-induced apoptosis in the cells.

Conclusion

VPA promotes the apoptosis of SH-SY5Y cells by activating miR-148a-3p/Mcl-1 signaling pathway.

关键词

Keywords

references

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