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，CG 1）是p53反式激活的靶基因，其生理和病理作用尚不清楚。在这里，我们证明，CG 1从细胞质易位到细胞核的神经元在各种损伤的反应。在正常成熟的啮齿动物脑中，几乎没有观察到CG 1免疫反应，然而，一些脑损伤显示出强烈的CG 1免疫反应在受损神经元的核中。在沙土鼠短暂性颈总动脉闭塞（CCAO）和小鼠大脑中动脉闭塞（MCAO）的缺血脑区，海马CA 1区神经元胞核内均可见较强的CG 1样免疫反应。TUNEL染色与CG 1阳性细胞不完全重叠，但与Fluoro-Jade B染色（变性标记物）高度重叠。由刀切、冷损伤和kinate注射引起的脑创伤也显示CG 1在位于损伤部位附近的神经元核中积聚。在p53缺陷小鼠中也获得了这些观察结果，表明CG 1在受损神经元中的积累是p53非依赖性的。在皮层神经元的原代培养中，当应用毒性水平的N-甲基-D-天冬氨酸（NMDA）时，证实了内源性CG 1的类似核转位。这些结果表明，CG 1从胞质区的核转位发生在损伤和变性的神经元中，不依赖于p53，CG 1核染色可以是一个很好的标记，神经元受到致命的损害。

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.