The p53-independent nuclear translocation of Cyclin G1 in degenerating neurons by ischemic and traumatic insults

细胞周期蛋白G1 （Cyclin G1, CG1）是p53转激活的靶基因，但其生理和病理作用尚不清楚。在这里，我们证明了CG1在各种损伤的反应中从细胞质转移到神经元核。在正常成熟的啮齿动物大脑中，几乎没有观察到CG1免疫反应；然而，一些脑损伤在受损神经元的细胞核中表现出强烈的CG1免疫反应性。沙鼠暂时性颈总动脉闭塞（CCAO）在海马CA1神经元中表现出较强的cg1样免疫反应性，小鼠永久性大脑中动脉闭塞（MCAO）在脑缺血区神经元核中表现出较强的cg1样免疫反应性。TUNEL染色与cg1阳性细胞不完全重叠，但与变性标志物Fluoro-Jade B染色高度重叠。刀伤、冷伤和kinate注射造成的脑外伤也显示CG1在损伤部位附近的神经元核中积累。这些观察结果在p53缺陷小鼠中也得到了，这表明CG1在受损神经元中的积累是与p53无关的。在皮质神经元原代培养中，当使用毒性水平的n -甲基-d-天冬氨酸（NMDA）时，内源性CG1也发生了类似的核易位。这些结果表明，受损和变性神经元胞质区CG1的核易位以不依赖p53的方式发生，CG1核染色可作为神经元遭受致死性损伤的良好标志。

Cyclin G1 (CG1) was identified as a p53-transactivated target gene, and yet its physiological and pathological roles have been unclear. Here, we demonstrate that CG1 is translocated from cytoplasm to the nuclei of neurons in response to variety of injuries. In the normalmatured rodent brain, CG1 immunoreactivity was hardly observed; however, some brain injuries exhibited intense CG1 immunoreactivity in the nuclei of the damaged neurons. Transient common carotid artery occlusion (CCAO) in the gerbil showed strong CG1-likeimmunoreactivity in the hippocampal CA1 neurons, and permanent middle cerebral artery occlusion (MCAO) in the mouse showed strong CG1-like immunoreactivity in the nuclei of neurons located in the ischemic brain regions. TUNEL staining did not exactly overlap with the CG1-positive cells, but overlapped highly with Fluoro-Jade B staining, a degeneration marker. Brain trauma caused by knife cut, cold injury, and kinate injection also showed CG1 accumulation in the neuronal nuclei located near the injury site. These observations were obtained in p53-deficient mice as well, suggesting that the accumulation of CG1 in the injured neurons is p53-independent. A similar nuclear translocation of endogenous CG1 was confirmed in a primary culture of cortical neurons when a toxic level of N-methyl-d-aspartate(NMDA) was applied. These results demonstrate that nuclear translocation of CG1 from cytoplasmic region occurs in damaged and degenerating neurons in a p53-independent manner, and the CG1 nuclear staining could be a good marker for the neurons received fatal damages.