title: MicroRNA-34c is regulated by p53 and is involved in sevoflurane-induced apoptosis in the developing rat brain potentially via the mitochondrial pathway.
abstract: The commonly used inhalation anesthetic, sevoflurane, has been previously demonstrated to induce apoptosis in the developing brain; however, the underlying molecular mechanisms remain largely unknown. MicroRNAs (miRNAs) serve important roles in multiple physiological/pathological processes, such as cell death and survival. In the present study, the miRNA sequence that was most closely associated with sevoflurane‑induced apoptosis in the hippocampus of neonatal rat brains was identified. Seven‑day‑old Sprague Dawley rats were first exposed to 2.3% sevoflurane for 6 h. Hippocampal brain tissues were harvested at 6 h following sevoflurane exposure. Cleaved caspase‑3 levels were examined using an immunofluorescence assay. Alterations in miRNA expression were assessed by microarray analysis and reverse transcription-quantitative polymerase chain reaction. The protein levels of p53, phosphorylated (p)‑p53, B-cell lymphoma-2 (Bcl-2) and Bax were assessed by western blot analysis. Sevoflurane exposure significantly increased the levels of cleaved caspase‑3 in the hippocampus. In addition, among the 688 miRNAs that were observed to be expressed in the hippocampus, sevoflurane exposure altered the expression levels of 266 miRNAs. Among these differentially expressed miRNAs, eight were significantly upregulated and one (miRNA‑34c) was significantly downregulated following sevoflurane exposure. Bioinformatics analyses indicated the miRNA‑34c was a direct downstream target of p53. Sevoflurane exposure induced significant alterations in the level of p‑p53, Bcl‑2 and Bax in the hippocampus of neonatal rats. In conclusion, the results of the present study suggest that miRNA‑34c may be regulated by p53 and is involved in sevoflurane‑induced neural apoptosis in the hippocampus of developing rat brains, potentially via the mitochondrial pathway.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Xian
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Jiehua
authors.initials: J
authors.lastname: Xia
authors.affiliation: Department of Anatomy, Zhong Shan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Hepatobiliary Surgery, The Sun Yat‑sen Memorial Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510120, P.R. China.
authors.forename: Wenda
authors.initials: W
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Zhibin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Dihan
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Feng
mesh_terms: D018685:Anesthetics, Inhalation / Q000633:toxicity*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D008297:Male; D008738:Methyl Ethers / Q000633:toxicity*; D035683:MicroRNAs / Q000235:genetics*; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D015398:Signal Transduction / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D018685:Anesthetics, Inhalation; C560944:MIRN34 microRNA, rat; D008738:Methyl Ethers; D035683:MicroRNAs; D016159:Tumor Suppressor Protein p53; D000077149:Sevoflurane; D053148:Caspase 3