Spatiotemporal Patterns of RING1 Expression after Rat Spinal Cord Injury

Spatiotemporal Patterns of RING1 Expression after Rat Spinal Cord Injury
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大鼠脊髓损伤后 RING1 表达的时空模式

DOI:
10.1007/s11064-016-2155-y
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发表时间:
2016-12
影响因子:
4.4
通讯作者:
Gong Leilei
Gong Leilei
中科院分区:
医学3区
文献类型:
--
作者:
Liu Hanzhang;Ji Wei;Gong Peipei;Liu Chun;Duan Chengwei;Gao Yilu;Liu Xiaojuan;Zhang Dongmei;Zhu Shunxing;Gong Leilei

文献摘要

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环指蛋白1(RING 1)是属于环指家族的具有RING结构域特征的蛋白质。它是一种E3泛素-蛋白连接酶,介导组蛋白H2 A的单泛素化,是多梳组蛋白(Polycomb group,PcG)抑制性多蛋白复合物PRC 1复合物的核心成分。研究表明RING 1基因通过促进细胞增殖发挥重要的致瘤作用,并在发育过程中维持转录程序的稳定性。然而,其对脊髓损伤(SCI)的作用机制尚不清楚。本研究通过建立大鼠急性脊髓损伤模型,研究RING 1的表达和功能。Western blot检测到RING 1蛋白表达于伤后第3天达高峰,随后逐渐下降。免疫组化结果显示RING 1在白色质中的表达较在灰质中明显增强。此外,通过免疫荧光双重染色,证实了损伤脊髓中RING 1和GFAP共表达的增加激活了星形胶质细胞。同时发现增殖细胞标志物PCNA与RING 1、GFAP共定位,提示RING 1可能参与了SCI后星形胶质细胞的增殖。在体外研究中,LPS刺激后C6细胞中RING 1蛋白水平增加,RING 1是LPS诱导星形胶质细胞增殖和活化所必需的。总之,我们对RING 1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。
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 rogram 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.