Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, People's Republic of China, 226001.
J Mol Neurosci. 2012 Jun;47(2):357-67. doi: 10.1007/s12031-012-9761-1. Epub 2012 May 9.
The cyclic AMP response element-binding protein (CREB) family can regulate biological functions of various types of cells by forming homo- or heterodimers to bind the target DNA sequences; it plays an essential role in individual neuronal function and entire neuronal circuits. One attractive activity of the CREB family is regulating the transcription of apoptosis-suppressor gene bcl-2. Cyclic AMP response element modulator-1 (CREM-1) is one member of the family with limited acquaintance. To investigate whether CREM-1 is involved in central nervous system injury and repair, we performed an acute traumatic brain injury (TBI) model in adult rats. Western blot analysis and immunohistochemistry showed a significant upregulation of CREM-1 in ipsilateral peritrauma cortex. Immunofluorescent labeling indicated that CREM-1 was localized mainly in the nuclei of neurons; co-localization of CREM-1 and active-caspase-3 in the ipsilateral cortex suggested that CREM-1 might participate in neuronal apoptosis. To further investigate the function of CREM-1, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of CREM-1 with p-CREB on PC12 cells by Western blot, immunofluorescent labeling, and co-immunoprecipitation. The result implied that the association of CREM-1 with p-CREB was enhanced in apoptotic cells. Additionally, knocking CREM-1 down with siRNA demonstrated the probable pro-apoptotic role played by CREM-1 in neuronal apoptosis. Together with our data, we hypothesized that CREM-1 might play an important role in regulating neuronal death after TBI by interacting with CREB.
环腺苷酸反应元件结合蛋白（CREB）家族可以通过形成同源或异源二聚体与靶 DNA 序列结合，调节各种类型细胞的生物学功能；它在单个神经元功能和整个神经元回路中起着至关重要的作用。CREB 家族的一项吸引人的活动是调节凋亡抑制基因 bcl-2 的转录。环腺苷酸反应元件调制器-1（CREM-1）是该家族的一个成员，人们对其了解有限。为了研究 CREM-1 是否参与中枢神经系统损伤和修复，我们在成年大鼠中进行了急性创伤性脑损伤（TBI）模型。Western blot 分析和免疫组织化学显示，同侧创伤皮质中 CREM-1 显著上调。免疫荧光标记表明 CREM-1 主要定位于神经元的细胞核中；同侧皮质中 CREM-1 和活性-caspase-3 的共定位表明 CREM-1 可能参与神经元凋亡。为了进一步研究 CREM-1 的功能，我们采用神经元细胞系 PC12 建立了凋亡模型。我们通过 Western blot、免疫荧光标记和共免疫沉淀分析了 CREM-1 与 p-CREB 在 PC12 细胞上的关联。结果表明，凋亡细胞中 CREM-1 与 p-CREB 的关联增强。此外，用 siRNA 敲低 CREM-1 表明 CREM-1 在神经元凋亡中可能发挥促凋亡作用。结合我们的数据，我们假设 CREM-1 可能通过与 CREB 相互作用在 TBI 后调节神经元死亡中发挥重要作用。
