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长链非编码RNA Gadd45a的上调与七氟醚诱导的大鼠神经干细胞神经毒性有关。

Upregulation of long noncoding RNA Gadd45a is associated with sevoflurane-induced neurotoxicity in rat neural stem cells.

作者信息

Lu Guolin, Xu Huali, Zhao Wei, Zhang Jianbo, Rao Dongdong, Xu Shiyuan

机构信息

Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province.

Departments of Anesthesiology.

出版信息

Neuroreport. 2018 May 23;29(8):605-614. doi: 10.1097/WNR.0000000000000980.

Abstract

Emerging evidence has shown that long noncoding RNA (lncRNA) plays a crucial role in controlling neural stem cells' (NSCs) survival. However, the fundamental role of lncRNA underlying sevoflurane-induced neurotoxicity remains poorly elucidated. In the present study, we investigate the effect of sevoflurane-induced neurotoxicity in a concentration-dependent and duration-dependent manner. Furthermore, we assayed the differential profile of lncRNA in rat hippocampal NSCs following sevoflurane exposure, and identified lncRNA Gadd45a and the correlation between lncRNA Gadd45a and Gadd45a. We found that lncRNA Gadd45a and its nearby gene, Gadd45a, were significantly upregulated in NSCs exposed to sevoflurane. Notably, Gadd45a was enriched in the cell cycle-relative pathway including mitogen-activated protein kinases and P53 signaling, whereas lncRNA Gadd45a was positively correlated with Gadd45a. These results suggest lncRNA Gadd45a is associated with sevoflurane-induced toxicity, and thus shed light on a new key target for revealing the molecular mechanism of sevoflurane-induced toxicity.

摘要

新出现的证据表明,长链非编码RNA(lncRNA)在控制神经干细胞(NSC)存活中起关键作用。然而,lncRNA在七氟醚诱导的神经毒性中所起的基本作用仍未得到充分阐明。在本研究中,我们以浓度依赖性和时间依赖性方式研究七氟醚诱导的神经毒性的影响。此外,我们检测了七氟醚暴露后大鼠海马神经干细胞中lncRNA的差异谱,并鉴定了lncRNA Gadd45a以及lncRNA Gadd45a与Gadd45a之间的相关性。我们发现,在暴露于七氟醚的神经干细胞中,lncRNA Gadd45a及其附近基因Gadd45a显著上调。值得注意的是,Gadd45a在包括丝裂原活化蛋白激酶和P53信号传导在内的细胞周期相关途径中富集,而lncRNA Gadd45a与Gadd45a呈正相关。这些结果表明lncRNA Gadd45a与七氟醚诱导的毒性有关,从而为揭示七氟醚诱导毒性的分子机制提供了一个新的关键靶点。

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