title: Aberrantly expressed long noncoding RNAs are involved in sevoflurane-induced developing hippocampal neuronal apoptosis: a microarray related study.
abstract: The commonly used volatile anesthetic sevoflurane has been shown to induce widespread apoptosis in the developing brain, yet the underlying molecular mechanisms are not fully understood. Accumulating research has demonstrated that long noncoding RNAs (lncRNAs) regulate multiple biological processes, including neural development, differentiation and apoptosis. They are aberrantly expressed in multiple neurodegenerative diseases. In this study, we employed a lncRNA-mRNA microarray analysis to determine whether and how lncRNAs are involved in sevoflurane-induced hippocampal neuronal apoptosis in neonatal mice. Our data showed that a single 6-h sevoflurane exposure of P7 mice resulted in significant morphological changes and apoptosis in the hippocampus. Moreover, the microarray simultaneously revealed 817 lncRNAs and 856 of their potential coding targets that related to apoptosis, of which 31 lncRNAs (19 up and 12 down) and 25 mRNAs were significantly differentially expressed (P < 0.05) after sevoflurane exposure. Importantly, we found that Bcl2l11 (BIM), which potentiates mitochondria-dependent apoptosis and its nearby enhancer-like lncRNA ENSMUST00000136025, were both more highly expressed in sevoflurane-treated samples compared with control samples. Subsequent qRT-PCR results confirmed the changes. Further CNC network indicated that lncRNA ENSMUST00000136025 was positively correlated with Bim. Moreover, sevoflurane induced a significant increase of pro-apoptotic protein BIM and Bax but a reduction of anti-apoptotic proteins Bcl-2 in the hippocampus. Our study first demonstrates that aberrantly expressed lncRNAs play a role in sevoflurane-induced hippocampal apoptosis. We noted that up-regulated ENSMUST00000136025 highly likely induced the over-expression of BIM, which eventually promoted mitochondria-mediated apoptosis. Such findings further broaden the understanding of molecular mechanisms responsible for sevoflurane-induced neurotoxicity.
authors.affiliation: Department of Anesthesiology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China.|Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Dihan
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Fujian Provincial Hospital, Fujian Provincial Clinical Medical College, Fujian Medical University, Fuzhou, 350001, China.
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China.
authors.forename: Wen
authors.initials: W
authors.lastname: He
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat-Sen University, No 58 zhongshan Road 2, Guangzhou, 510080, China. fengxiar1968@163.com.
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
mesh_terms: D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015870:Gene Expression; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D040081:Protein Array Analysis / Q000379:methods; D062085:RNA, Long Noncoding / Q000096:biosynthesis* / Q000235:genetics; D011897:Random Allocation; D000077149:Sevoflurane
chemical_list: D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D062085:RNA, Long Noncoding; D000077149:Sevoflurane
keywords: Apoptosis; Hippocampus; LncRNAs; Microarray; Sevoflurane