Trim47 is a critical regulator of cerebral ischemia-reperfusion injury through regulating apoptosis and inflammation
Trim47 is a critical regulator of cerebral ischemia-reperfusion injury through regulating apoptosis and inflammation
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DOI：
10.1016/j.bbrc.2019.05.065
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发表时间：
2019-08-06
影响因子：
3.1
通讯作者：
Xue, Rui-Wen
中科院分区：
文献类型：
--
作者：
Hao, Miao-Qing;Xie, Lan-Jun;Xue, Rui-Wen
脑缺血是世界上导致死亡和长期残疾的主要原因。Trim 47是TRIM家族蛋白质中的一员，参与多种疾病的细胞凋亡和炎症反应。然而，Trim 47在脑缺血/再灌注（I/R）损伤中的潜在分子机制仍不清楚。本研究旨在探讨Trim 47在脑I/R损伤中的作用及其可能机制。结果表明，Trim 47表达在中风发作后的大鼠中被显著诱导。通过遗传学方法，我们发现Trim 47基因敲低可显著减少大脑中动脉闭塞（MCAO）所致脑I/R损伤大鼠的梗死面积，减轻神经功能缺损评分，降低脑含水量。此外，Trim 47敲低减轻脑I/R与通过抑制Caspase-3裂解抑制细胞凋亡相关。此外，减少Trim 47明显减少了MCAO大鼠脑样品中促炎因子的释放，包括白细胞介素6（IL-6）、肿瘤坏死因子-α（INF-α）和诱导型一氧化氮合酶（iNOS），这部分是通过阻断核因子-κ B（NF-κ B）信号传导实现的。然而，Trim 47过表达通过促进细胞凋亡和炎症反应而明显加速脑缺血损伤。Trim 47敲低对脑I/R的抑制作用在由氧和葡萄糖剥夺（OGD）刺激的人神经元样细胞中得到验证。因此，本研究证明了Trim 47对脑I/R损伤的作用的新机制，并且靶向Trim 47可能为中风治疗提供可行的疗法。(C)2019由Elsevier Inc.出版
Cerebral ischemia is a leading cause of death and long-term disability in the world. Tripartite motif-47 (Trim47), a member of the TRIM family proteins, has been reported to be involved in apoptosis and inflammation in various types of diseases. Nevertheless, the underlying molecular mechanism of Trim47 in cerebral ischemia/reperfusion (I/R) injury remains unclear. This study aimed to explore the role of Trim47 in cerebral I/R injury and the potential underlying mechanisms. The results indicated that Trim47 expression was markedly induced in rats after stroke onset. By the use of genetic approaches, we indicated that Trim47 knockdown significantly reduced the infarct size, mitigated the neurological deficits scores and decreased brain water contents in rats with cerebral I/R injury induced by middle cerebral artery occlusion (MCAO). In addition, Trim47 knockdown-alleviated cerebral I/R was correlated with the suppression of apoptosis through inhibiting Caspase-3 cleavage. Furthermore, reducing Trim47 apparently decreased the release of pro-inflammatory factors, including interleukin 6 (IL-6), tumor necrosis factor-alpha (INF-alpha) and inducible nitric oxide synthase (iNOS), in brain samples of MCAO rats, which was partly by the blockage of nuclear factor-kappa B (NF-kappa B) signaling. However, Trim47 over-expression markedly accelerated cerebral ischemia injury through promoting apoptosis and inflammation. The suppressive effects of Trim47 knockdown on cerebral I/R were verified in human neuron-like cells stimulated by oxygen and glucose deprivation (OGD). Thus, this study demonstrated a new mechanism for the effect of Trim47 on cerebral I/R injury, and targeting Trim47 might provide feasible therapies for stroke treatment. (C) 2019 Published by Elsevier Inc.