Expression of Sam68 Associates with Neuronal Apoptosis and Reactive Astrocytes After Spinal Cord Injury
Expression of Sam68 Associates with Neuronal Apoptosis and Reactive Astrocytes After Spinal Cord Injury
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DOI：
10.1007/s10571-016-0384-x
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发表时间：
2017-04-01
影响因子：
4
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Chen, Xinlei;Liu, Lei;Zhang, Feng
有丝分裂相关的Src蛋白（Sam68；68 kDa）是一种新型的RNA结合蛋白，属于参与多种生物过程的RNA信号转导和激活家族。然而，Sam68在中枢神经系统中的表达及作用仍不清楚。在本研究中，我们在成年大鼠中建立了脊髓损伤（SCI）模型，发现该模型中Sam68蛋白水平显著升高，在脊髓损伤后第3天达到峰值，然后在第14天逐渐恢复到正常水平。我们利用免疫组织化学分析揭示了Sam68在脊髓中广泛分布。此外，双重免疫荧光染色显示Sam68免疫反应性主要在神经元和星形胶质细胞中发现。而且，在神经元细胞核中分别检测到Sam68/活化的半胱天冬酶 - 3的共定位，在胶质纤维酸性蛋白中检测到Sam68/增殖细胞核抗原（PCNA）的共定位。在体外，我们发现通过小干扰RNA耗尽Sam68可抑制神经元凋亡和星形胶质细胞增殖，并降低细胞周期蛋白D1蛋白水平。总之，这是首次发现Sam68在脊髓损伤中表达的研究。我们的结果表明，Sam68可能在脊髓损伤后神经元的凋亡和星形胶质细胞的增殖中起作用。这项研究将为脊髓损伤的临床治疗提供新的药物靶点。
Src-associated in mitosis (Sam68; 68 kDa) is a novel RNA-binding protein that belongs to the signal transduction and activation of RNA family involved in various biological processes. However, the expression and roles of Sam68 in the central nervous system remain unknown. In the present study, we performed a spinal cord injury (SCI) model in adult rats and found a significant increase of Sam68 protein levels in this model, which reached a peak at day 3 and then gradually returned to normal levels at day 14 after SCI. We use immunohistochemistry analysis revealing a widespread distribution of Sam68 in the spinal cord. In addition, double-immunofluorescence staining showed that Sam68 immunoreactivity was found predominantly in neurons and astrocytes. Moreover, colocalization of Sam68/active caspase-3 has been respectively detected in neuronal nuclei, and colocalization of Sam68/PCNA has been detected in glial fibrillary acidic protein. In vitro, we found that depletion of Sam68 by short interfering RNA inhibits neuronal apoptosis and astrocyte proliferation and decreases cyclin D1 protein levels. In conclusion, this is the first study to find the Sam68 expression in SCI. Our results suggest that Sam68 might be illustrated in the apoptosis of neurons and proliferation of astrocytes after SCI. This research will provide new drug targets for clinical treatment of SCI.