Isoflurane Increases Neuronal Cell Death Vulnerability by Downregulating miR-214

PLoS One

Hoau-Yan Wang¹  Yan Zhang²  Kuo-Chieh Lee³  Tao Xu³  Hailiang Yan⁴  Hongfeng Zhao⁴ 

[1] Beijing No.4 High School, Beijing, China;Department of Pharmacology, Physiology and Neuroscience, Sophie Davis School of Biomedical Education/City University of New York Medical School, New York, New York, United States of America;Department of Urology, Peking University People’s Hospital, Beijing, China;State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China

关键词: Neuronal death;    Neurons;    Anesthetics;    Alzheimer's disease;    Cell death;    Small interfering RNAs;    MicroRNAs;    Cytotoxicity;   

DOI  :  10.1371/journal.pone.0055276

学科分类：医学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY