Upregulation of long noncoding RNA Gadd45a is associated with sevoflurane-induced neurotoxicity in rat neural stem cells
Upregulation of long noncoding RNA Gadd45a is associated with sevoflurane-induced neurotoxicity in rat neural stem cells
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DOI：
10.1097/wnr.0000000000000980
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发表时间：
2018-05-23
期刊：
影响因子：
1.7
通讯作者：
Xu, Shiyuan
中科院分区：
文献类型：
--
作者：
Lu, Guolin;Xu, Huali;Xu, Shiyuan
新的证据表明，长链非编码RNA（lncRNA）在控制神经干细胞（NSCs）的存活中起着至关重要的作用。然而，lncRNA在七氟烷诱导的神经毒性中的基本作用仍不清楚。在本研究中，我们以浓度依赖性和持续时间依赖性的方式研究了七氟烷诱导的神经毒性的作用。此外，我们还检测了七氟醚暴露后大鼠海马神经干细胞中lncRNA的差异表达，并鉴定了lncRNA Gadd45a及其与Gadd45a的相关性。我们发现lncRNA Gadd45a及其邻近基因Gadd45a在暴露于七氟烷的NSC中显著上调。值得注意的是，Gadd45a在细胞周期相关途径中富集，包括促分裂原活化蛋白激酶和P53信号传导，而lncRNA Gadd45a与Gadd45a正相关。这些结果表明lncRNA Gadd45a与七氟醚诱导的毒性相关，从而为揭示七氟醚诱导毒性的分子机制提供了新的关键靶点。版权所有（C）2018威科医疗集团All rights reserved.
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. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.