title: Isoflurane increases neuronal cell death vulnerability by downregulating miR-214.
abstract: Since accumulating evidence suggests the application of anesthetics may increase the risk of Alzheimer's disease (AD), we investigated the cytotoxicity of inhaled general anesthesia in neurons and its underlying mechanism. Using primary cultured rat hippocampal neurons as the study model, here we show that isoflurane increases vulnerability to intracellular or extracellular amyloid β with or without serum deprivation. This isoflurane-induced effect is mediated by the downregulation of miR-214 level that lead to an elevated expression of Bax, a prominent target for miR-214. We conclude that isoflurane increases cell death in the presence of amyloid β by increasing Bax level through downregulating miR-214. Our data provide a new insight for inhaled anesthetics toxicity and indicate a possible mechanistic link between anesthetic application and neurodegenration in AD.
authors: State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China.
authors: Hailiang
authors: H
authors: Yan
authors: Tao
authors: T
authors: Xu
authors: Hongfeng
authors: H
authors: Zhao
authors: Kuo-Chieh
authors: KC
authors: Lee
authors: Hoau-Yan
authors: HY
authors: Wang
authors: Yan
authors: Y
authors: Zhang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016923:Cell Death; D002478:Cells, Cultured; D015536:Down-Regulation; D007530:Isoflurane / Q000494:pharmacology*; D035683:MicroRNAs / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C548144:MIRN124 microRNA, rat; D035683:MicroRNAs; D051028:bcl-2-Associated X Protein; D007530:Isoflurane