Up-regulation of Smurf1 after spinal cord injury in adult rats
Up-regulation of Smurf1 after spinal cord injury in adult rats
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成年大鼠脊髓损伤后 Smurf1 的上调
DOI：
10.1007/s10735-013-9499-2
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发表时间：
2013-08-01
影响因子：
3.2
通讯作者：
Cui, Zhiming
中科院分区：
文献类型：
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作者：
Li, Debao;Zhang, Jinlong;Cui, Zhiming
Smad泛素化调节因子1（Smurf 1）是Hect蛋白家族的成员之一，该家族还包括泛素E3型连接酶Nedd 3和E6-AP。作为一种E3连接酶，Smurf 1选择性地与受体调节的Smads相互作用，触发它们的泛素化和降解。最近有研究表明Smurf 1可以通过负调控p53来抑制细胞凋亡，这依赖于Smurf 1稳定MDM 2-MDMX复合物的作用。然而，Smurf 1在中枢神经系统损伤中的作用仍不清楚。本研究采用成年大鼠急性脊髓损伤模型，研究Smurf 1在脊髓中的蛋白表达和细胞定位。Western blot分析显示Smurf 1在正常脊髓中呈低表达。脊髓损伤后6 h开始升高，1d达高峰，持续3d，以后逐渐下降。免疫组化进一步证实，Smurf 1免疫活性在正常情况下在灰质和白色物质中以低水平表达，并且在SCI后增加。免疫荧光双标染色显示，Smurf 1在损伤后1天与NeuN（神经元标记物）、CNR（少突胶质细胞标记物）和活性caspase-3共表达。此外，SCI后p53和MDM 2水平持续上调。这些结果提示Smurf 1可能参与了脊髓损伤后的病理生理过程。
Smad ubiquitination regulatory factor 1 (Smurf1) is one of members of the Hect family of proteins, which also includes the ubiquitin E3-type ligases Nedd3 and E6-AP. As an E3 ligase, Smurf1 selectively interacts with receptor-regulated Smads to trigger their ubiquitination and degradation. Recently, a report indicates that Smurf1 can inhibit apoptosis by regulating p53 negatively, which depends on the effect of Smurf1 stabilizing the MDM2-MDMX complex. However, the roles of Smurf1 in central nervous system injury remain to be unknown. In our study, we finished acute spinal cord injury (SCI) in adult rats to research the protein expression and cellular localization of Smurf1 in spinal cord. Western blot analysis showed that Smurf1 was low expressed in normal spinal cord. It was increased at 6 h after SCI, peaked at 1 day, remained for 3 days, and then declined gradually during the following days. Immunohistochemistry further confirmed that Smurf1 immunoactivity was expressed at low levels in the gray matter and white matter in normal condition and increased after SCI. Double immunofluorescence staining showed that Smurf1 was co-expressed NeuN (neuronal marker), CNPase (oligodendroglial marker), and active caspase-3 at 1 day post-injury. Additionally, p53 and MDM2 levels were up-regulated after SCI consistently. All these findings suggest that Smurf1 might be involved in the pathophysiology of spinal cord after SCI.