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大鼠脊髓损伤后RING1表达的时空模式

Spatiotemporal Patterns of RING1 Expression after Rat Spinal Cord Injury.

作者信息

Liu Hanzhang, Ji Wei, Gong Peipei, Liu Chun, Duan Chengwei, Gao Yilu, Liu Xiaojuan, Zhang Dongmei, Zhu Shunxing, Gong Leilei

机构信息

Morphology Laboratory, Medical College of Nantong University, Nantong, 226001, Jiangsu, China.

Key Laboratory of Nerve Regeneration, Nantong University, Nantong, 226001, Jiangsu, China.

出版信息

Neurochem Res. 2017 Apr;42(4):1191-1201. doi: 10.1007/s11064-016-2155-y. Epub 2016 Dec 28.

Abstract

Ring finger protein 1 (RING1) is a RING domain characterized protein belonging to the RING finger family. It is an E3 ubiquitin-protein ligase that mediated monoubiquitination of histone H2A and the core component of PRC1 complex, which is the repressive multiprotein complex of Polycomb group (PcG). Previous studies showed the important tumorigenic role of RING1 via promoting cell proliferation and the crucial function in maintaining transcriptional program stability during development. However, its mechanism for spinal cord injury (SCI) is still unknown. In our research, we established an acute SCI model in adult rats and studied the expression and function profiles of RING1. RING1 protein level detected by western blot peaked at day 3 after trauma and then decreased gradually. Immunohistochemistry showed the increase of RING1 expression displayed in the white matter more obviously than in the gray matter. Furthermore, increased co-expression of RING1 and GFAP confirmed activated astrocytes in injured spinal cord via double immunofluorescence staining. Meanwhile, we also found the co-localization of PCNA, a famous marker of proliferative cells, with RING1 and GFAP, which indicated RING1 might play a role in astrocyte proliferation after SCI. In vitro studies, RING1 protein level in C6 cells increased after LPS challenge and RING1 was required for astrocyte proliferation and activation induced by LPS. In summary, we took a new insight into the function of RING1 in the cellular and molecular mechanism underlying the pathophysiology of SCI.

摘要

无名指蛋白1(RING1)是一种具有RING结构域特征的蛋白质,属于RING指家族。它是一种E3泛素蛋白连接酶,介导组蛋白H2A的单泛素化,是PRC1复合物的核心成分,PRC1复合物是多梳蛋白家族(PcG)的抑制性多蛋白复合物。先前的研究表明,RING1通过促进细胞增殖在肿瘤发生中发挥重要作用,并且在发育过程中维持转录程序稳定性方面具有关键功能。然而,其在脊髓损伤(SCI)中的机制仍不清楚。在我们的研究中,我们在成年大鼠中建立了急性SCI模型,并研究了RING1的表达和功能概况。通过蛋白质印迹法检测到的RING1蛋白水平在创伤后第3天达到峰值,然后逐渐下降。免疫组织化学显示,RING1表达的增加在白质中比在灰质中更明显。此外,通过双重免疫荧光染色,RING1与GFAP共表达增加证实了损伤脊髓中星形胶质细胞的激活。同时,我们还发现增殖细胞的著名标志物PCNA与RING1和GFAP共定位,这表明RING1可能在SCI后星形胶质细胞增殖中发挥作用。在体外研究中,LPS刺激后C6细胞中的RING1蛋白水平升高,并且RING1是LPS诱导的星形胶质细胞增殖和激活所必需的。总之,我们对RING1在SCI病理生理学的细胞和分子机制中的功能有了新的认识。

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