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

Lu, Guolina,b,*; Xu, Hualia,*; Zhao, Weia; Zhang, Jianboa; Rao, Dongdongc; Xu, Shiyuana

doi: 10.1097/WNR.0000000000000980
Cellular, Molecular and Developmental Neuroscience

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.

aDepartment of Anesthesiology, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong Province

Departments of bAnesthesiology

cClinical Laboratory, Fujian Provincial Maternity and Children’s Hospital, Fujian Medical University, Fuzhou, Fujian Province, China

* Guolin Lu and Huali Xu contributed equally to the writing of this article.

Correspondence to Shiyuan Xu, MD, Department of Anesthesiology, Zhujiang Hospital, Southern Medical University, 253 Industrial Road, Guangzhou 510282, Guangdong Province, China Tel: +86 136 097 27860; fax: +86 020 616 43298; e-mail: xsy998@smu.edu.cn

Received December 3, 2017

Accepted January 8, 2018

© 2018 Wolters Kluwer Health | Lippincott Williams & Wilkins