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Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2

Duration of surgical general anaesthesia is associated with severe brain injury and neurological deficits. The specific mechanisms underlying post‐general anaesthesia brain injury, however, still remain to be elucidated. Herein, we explore the role of microRNA‐214 (miR‐214) in the occurrence of brai...

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Autores principales: Liu, Tiejun, Wang, Bin, Li, Gai, Dong, Xiaoliu, Yu, Guannan, Qian, Qingzeng, Duan, Likun, Li, Hongxia, Jia, Zhao, Bai, Jing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753869/
https://www.ncbi.nlm.nih.gov/pubmed/33147380
http://dx.doi.org/10.1111/jcmm.15222
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author Liu, Tiejun
Wang, Bin
Li, Gai
Dong, Xiaoliu
Yu, Guannan
Qian, Qingzeng
Duan, Likun
Li, Hongxia
Jia, Zhao
Bai, Jing
author_facet Liu, Tiejun
Wang, Bin
Li, Gai
Dong, Xiaoliu
Yu, Guannan
Qian, Qingzeng
Duan, Likun
Li, Hongxia
Jia, Zhao
Bai, Jing
author_sort Liu, Tiejun
collection PubMed
description Duration of surgical general anaesthesia is associated with severe brain injury and neurological deficits. The specific mechanisms underlying post‐general anaesthesia brain injury, however, still remain to be elucidated. Herein, we explore the role of microRNA‐214 (miR‐214) in the occurrence of brain injury after general anaesthesia and its underlying mechanism. Hippocampal tissues and neurons were isolated from rats exposed to 2% sevoflurane. TUNEL stains reflect hippocampal neuron apoptosis. Cultured hippocampal neurons stained with JC‐1 and MitoTracker dyes were imaged by fluorescence microscope to visualize changes of mitochondrial membrane potential and mitochondrial fusion. Mitochondrial function was evaluated. Mitofusin 2 (Mfn2) binding to miR‐214 or pyruvate kinase M2 (Pkm2) was confirmed by co‐immunoprecipitation, immunofluorescence, dual luciferase reporter gene and RNA immunoprecipitation assays. After exposure to 2% sevoflurane, up‐regulated miR‐214 expression and impaired interaction between Mfn2 and Pkm2 were found in rat hippocampal tissues. Rats exposed to 2% sevoflurane also experienced neuronal injury, mitochondrial defects and deficits in the brain‐derived neurotrophic factor (Bdnf) signalling. miR‐214 was shown to target Mfn2 by impairing its binding with Pkm2. Inhibiting miR‐214 expression using its specific inhibitor improved mitochondrial membrane potential, enhanced mitochondrial fusion, maintained mitochondrial function, restored interaction between Mfn2 and Pkm2, and activated the Bdnf signalling in cultured hippocampal neurons. Adenovirus infection of miR‐214 inhibitor reduced neuron apoptosis and maintained mitochondrial function in the hippocampus of rats exposed to 2% sevoflurane. Taken together, the study demonstrates inhibition of miR‐214 is cerebral protective against brain injury following general anaesthesia.
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spelling pubmed-77538692020-12-23 Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2 Liu, Tiejun Wang, Bin Li, Gai Dong, Xiaoliu Yu, Guannan Qian, Qingzeng Duan, Likun Li, Hongxia Jia, Zhao Bai, Jing J Cell Mol Med Original Articles Duration of surgical general anaesthesia is associated with severe brain injury and neurological deficits. The specific mechanisms underlying post‐general anaesthesia brain injury, however, still remain to be elucidated. Herein, we explore the role of microRNA‐214 (miR‐214) in the occurrence of brain injury after general anaesthesia and its underlying mechanism. Hippocampal tissues and neurons were isolated from rats exposed to 2% sevoflurane. TUNEL stains reflect hippocampal neuron apoptosis. Cultured hippocampal neurons stained with JC‐1 and MitoTracker dyes were imaged by fluorescence microscope to visualize changes of mitochondrial membrane potential and mitochondrial fusion. Mitochondrial function was evaluated. Mitofusin 2 (Mfn2) binding to miR‐214 or pyruvate kinase M2 (Pkm2) was confirmed by co‐immunoprecipitation, immunofluorescence, dual luciferase reporter gene and RNA immunoprecipitation assays. After exposure to 2% sevoflurane, up‐regulated miR‐214 expression and impaired interaction between Mfn2 and Pkm2 were found in rat hippocampal tissues. Rats exposed to 2% sevoflurane also experienced neuronal injury, mitochondrial defects and deficits in the brain‐derived neurotrophic factor (Bdnf) signalling. miR‐214 was shown to target Mfn2 by impairing its binding with Pkm2. Inhibiting miR‐214 expression using its specific inhibitor improved mitochondrial membrane potential, enhanced mitochondrial fusion, maintained mitochondrial function, restored interaction between Mfn2 and Pkm2, and activated the Bdnf signalling in cultured hippocampal neurons. Adenovirus infection of miR‐214 inhibitor reduced neuron apoptosis and maintained mitochondrial function in the hippocampus of rats exposed to 2% sevoflurane. Taken together, the study demonstrates inhibition of miR‐214 is cerebral protective against brain injury following general anaesthesia. John Wiley and Sons Inc. 2020-11-04 2020-12 /pmc/articles/PMC7753869/ /pubmed/33147380 http://dx.doi.org/10.1111/jcmm.15222 Text en © 2020 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Tiejun
Wang, Bin
Li, Gai
Dong, Xiaoliu
Yu, Guannan
Qian, Qingzeng
Duan, Likun
Li, Hongxia
Jia, Zhao
Bai, Jing
Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
title Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
title_full Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
title_fullStr Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
title_full_unstemmed Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
title_short Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
title_sort disruption of microrna‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting mfn2 interaction with pkm2
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753869/
https://www.ncbi.nlm.nih.gov/pubmed/33147380
http://dx.doi.org/10.1111/jcmm.15222
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