Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2
| العنوان: | Disruption of microRNA‐214 during general anaesthesia prevents brain injury and maintains mitochondrial fusion by promoting Mfn2 interaction with Pkm2 |
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| المؤلفون: | Hongxia Li, Xiaoliu Dong, Tiejun Liu, Bin Wang, Qingzeng Qian, Zhao Jia, Gai Li, Jing Bai, Guannan Yu, Likun Duan |
| المصدر: | Journal of Cellular and Molecular Medicine |
| بيانات النشر: | John Wiley and Sons Inc., 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Cell Respiration, Pyruvate Kinase, MFN2, Hippocampus, Gene Expression, microRNA‐214, Hippocampal formation, PKM2, Anesthesia, General, Mitochondrial Dynamics, Oxidative Phosphorylation, GTP Phosphohydrolases, Mitochondrial Proteins, 03 medical and health sciences, Mitofusin-2, 0302 clinical medicine, Neurotrophic factors, Mitofusin 2, Animals, general anaesthesia, Chemistry, Cell Biology, Original Articles, brain injury, Cell biology, Mitochondria, Rats, Disease Models, Animal, MicroRNAs, 030104 developmental biology, mitochondrial fusion, Gene Expression Regulation, Apoptosis, 030220 oncology & carcinogenesis, Brain Injuries, Molecular Medicine, Original Article, RNA Interference, pyruvate kinase M2, Oxidation-Reduction, Protein Binding |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1582-4934 1582-1838 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5e8e0ff11f2c53371b7b47bb1048198Test http://europepmc.org/articles/PMC7753869Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....a5e8e0ff11f2c53371b7b47bb1048198 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15824934 15821838 |
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