神经保护
基因敲除
细胞凋亡
脊髓损伤
HDAC3型
基因沉默
标记法
脊髓
药理学
化学
生物
细胞生物学
医学
组蛋白脱乙酰基酶
神经科学
生物化学
组蛋白
基因
作者
Qiang Zhou,Xiaolan Feng,Fei Ye,Fei Lei,Xufeng Jia,Daxiong Feng
出处
期刊:Life Sciences
[Elsevier]
日期:2020-11-01
卷期号:260: 118098-118098
被引量:10
标识
DOI:10.1016/j.lfs.2020.118098
摘要
Spinal cord injury (SCI) is one of the most devastating diseases that challenges neurology and medicine, leading to paraplegia or quadriplegia worldwide. Neuroprotection conferred by histone deacetylase (HDAC) inhibitors against various insults and deficits in the central nervous system has been reported previously. Herein, we set out to ascertain whether HDAC3 inhibition exerts neuroprotective effects against SCI. A modified Allen's weight-drop method was performed to induce experimental SCI in rats. Basso-Beattie-Bresnahan (BBB) scores were used to assess locomotor function. Flow cytometric analysis of AnnexinV-FITC/PI double staining, TUNEL staining, and immunoblotting analysis of apoptosis-related proteins were performed to determine apoptosis in H2O2-induced cell injury of primary rat neurons. Upregulated HDAC3 and downregulated miR-27a were observed in spinal cord tissues of SCI rats and H2O2-injured neurons. HDAC3 knockdown by its specific shRNA restored the locomotor function of SCI rats and prevented rat neurons from H2O2-induced apoptosis through promotion of miR-27a. miR-27a targeted PAK6 (encoding P21-activated kinase 6) and inhibited its expression. The effects of HDAC3 knockdown on the locomotor function of SCI rats and H2O2-induced apoptosis of rat neurons were lost upon further PAK6 overexpression. The present study uncovers that silencing HDAC3 inhibited PAK6 expression by upregulating miR-27a, eventually inhibiting neuron apoptosis and promoting the recovery of SCI, which might provide a novel therapeutic target for SCI.
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