The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by ischemic and traumatic insults
The p53-independent nuclear translocation of cyclin G1 in degenerating neurons by ischemic and traumatic insults
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DOI：
10.1016/j.expneurol.2005.01.018
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发表时间：
2005-06-01
影响因子：
5.3
通讯作者：
Kiyama, H
中科院分区：
文献类型：
--
作者：
Maeda, M;Ampo, KI;Kiyama, H
Cyclin G1 (CG1) 被确定为 p53 反式激活的靶基因，但其生理和病理作用尚不清楚。在这里，我们证明 CG1 响应各种损伤而从神经元的细胞质转移到细胞核。在正常成熟的啮齿动物大脑中，几乎观察不到CG1免疫反应性；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。沙鼠的短暂颈总动脉闭塞（CCAO）在海马 CA1 神经元中显示出强烈的 CG1 样免疫反应性，而小鼠的永久性大脑中动脉闭塞（MCAO）在位于缺血脑区域的神经元细胞核中显示出强烈的 CG1 样免疫反应性。 TUNEL 染色与 CG1 阳性细胞并不完全重叠，但与变性标记 Fluoro-Jade B 染色高度重叠。刀割、冷伤和肌肽注射造成的脑外伤也显示出 CG1 在损伤部位附近的神经元核中积聚。这些观察结果也在 p53 缺陷小鼠中获得，表明受损神经元中 CG1 的积累与 p53 无关。当应用有毒水平的 N-甲基-D-天冬氨酸 (NMDA) 时，在皮质神经元的原代培养物中证实了内源性 CG1 的类似核易位。这些结果表明，受损和退化神经元中的 CG1 以不依赖于 p53 的方式从细胞质区域发生核转位，并且 CG1 核染色可能是受到致命损伤的神经元的良好标记。 (c) 2005 Elsevier Inc. 保留所有权利。
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 normal matured 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-like immunoreactivity 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. (c) 2005 Elsevier Inc. All rights reserved.