Department of Orthopaedics, Second Affiliated Hospital of Nantong University, Nantong 226002, Jiangsu, People's Republic of China.
J Mol Histol. 2013 Apr;44(2):147-58. doi: 10.1007/s10735-013-9481-z. Epub 2013 Jan 31.
Phosphorylated retinoblastoma protein (p-Rb), a well identified cell cycle related protein, is involved in regulating the biological functions of various cell types including neurons. One attractive biological function of p-Rb is releasing E2F transcription factor to induce S-phase entry and cellular proliferation of mitotic cells. However, some studies point out that the role of p-Rb in post-mitotic cells such as mature neurons is unique; it may induce cellular apoptosis rather than proliferation via regulating cell cycle reactivation. Up to now, the knowledge of p-Rb function in CNS is still limited. To investigate whether p-Rb is involved in CNS injury and repair, we performed a traumatic brain injury model in adult rats. Up-regulation of p-Rb was observed in the injured brain cortex by western blot analysis and immunohistochemistry staining. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) and 4',6-diamidino-2-phenylindole (DAPI) staining suggested that p-Rb was relevant to neuronal apoptosis after brain injury. In addition, glutamate excitotoxic model of primary cortex neurons was introduced to further investigate the role of p-Rb in neuronal apoptosis; the result implied p-Rb was associated with cell cycle activation in the apoptotic neurons. Based on our data, we suggested that p-Rb might play an important role in neuronal apoptosis after traumatic brain injury in rat; which might also provide a basis for the further study on its role in regulating cell cycle re-entry in apoptotic neurons, and might gain a novel strategy for the clinical therapy for traumatic brain injury.
磷酸化视网膜母细胞瘤蛋白(p-Rb)是一种众所周知的细胞周期相关蛋白,参与调节包括神经元在内的各种细胞类型的生物学功能。p-Rb 的一个有吸引力的生物学功能是释放 E2F 转录因子,以诱导有丝分裂细胞的 S 期进入和细胞增殖。然而,一些研究指出,p-Rb 在有丝分裂后细胞(如成熟神经元)中的作用是独特的;它可能通过调节细胞周期再激活来诱导细胞凋亡而不是增殖。到目前为止,p-Rb 在中枢神经系统中的功能知识仍然有限。为了研究 p-Rb 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创伤性脑损伤模型。Western blot 分析和免疫组织化学染色观察到损伤大脑皮层中 p-Rb 的上调。末端脱氧核苷酸转移酶脱氧-UTP-切口末端标记(TUNEL)和 4',6-二脒基-2-苯基吲哚(DAPI)染色表明,p-Rb 与脑损伤后神经元凋亡有关。此外,还引入了原代皮质神经元谷氨酸兴奋性毒性模型,以进一步研究 p-Rb 在神经元凋亡中的作用;结果表明 p-Rb 与凋亡神经元中的细胞周期激活有关。基于我们的数据,我们认为 p-Rb 可能在大鼠创伤性脑损伤后的神经元凋亡中发挥重要作用;这也可能为进一步研究其在调节凋亡神经元中细胞周期再进入的作用提供基础,并可能为创伤性脑损伤的临床治疗获得一种新策略。