Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, 226001, People's Republic of China.
J Mol Neurosci. 2013 Sep;51(1):208-18. doi: 10.1007/s12031-013-9994-7. Epub 2013 Mar 15.
Traumatic brain injury (TBI) initiates a complex series of neurochemical and signaling changes that leads to neuronal dysfunction and over-reactive astrocytes. There is increasing evidence that CRM1 mediated P27(Kip1), which is a potent inhibitor of G1 cyclin-dependent kinases complexes, nuclear export-dependent or -independent Jab1/CSN5, and cytoplasmic degradation in cells. Up to now, the function of CRM1 in central nervous system (CNS) is still with limited acquaintance. In our study, to investigate whether CRM1 is involved in CNS lesion, we performed a TBI model in adult rats. Western blot and RT-PCR analysis revealed that the level of protein and mRNA of CRM1 increased in ipsilateral brain cortex in comparison to the contralateral. Immunohistochemistry and immunofluorescence double labeling indicated that CRM1 was shutting into nucleus around the wound, and increased CRM1 co-localized with P27(Kip1). Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) staining suggested that CRM1 was involved in neuronal apoptosis after brain injury. We also investigated co-localization of CRM1 and active-caspase-3 in the ipsilateral brain cortex. In addition, the expression patterns of Bax and active-caspase-3 were parallel with that of CRM1. Based on our data, we suggested that CRM1 might play an important role in neuronal apoptosis following TBI, and might provide a basis for the further study on its role in regulating the expression of P27(Kip1) and cell cycle re-entry in TBI.
创伤性脑损伤（TBI）引发了一系列复杂的神经化学和信号变化，导致神经元功能障碍和过度活跃的星形胶质细胞。越来越多的证据表明，CRM1 介导的 P27（Kip1），它是 G1 周期蛋白依赖性激酶复合物的有效抑制剂，依赖或不依赖核输出的 Jab1/CSN5，以及细胞内的降解。到目前为止，CRM1 在中枢神经系统（CNS）中的功能仍然知之甚少。在我们的研究中，为了研究 CRM1 是否参与中枢神经系统损伤，我们在成年大鼠中建立了 TBI 模型。Western blot 和 RT-PCR 分析显示，与对侧相比，损伤侧大脑皮质中 CRM1 的蛋白和 mRNA 水平增加。免疫组织化学和免疫荧光双重标记表明，CRM1 围绕伤口进入核内，并且增加的 CRM1 与 P27（Kip1）共定位。末端脱氧核苷酸转移酶脱氧-UTP-缺口末端标记（TUNEL）染色表明，CRM1 参与脑损伤后的神经元凋亡。我们还研究了 CRM1 和活性-caspase-3 在损伤侧大脑皮质中的共定位。此外，Bax 和活性-caspase-3 的表达模式与 CRM1 的表达模式平行。基于我们的数据，我们认为 CRM1 可能在 TBI 后神经元凋亡中发挥重要作用，并为进一步研究其在调节 TBI 中 P27（Kip1）表达和细胞周期再进入中的作用提供依据。
