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Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity:a mechanistic pathway

Neural Regeneration Research 2018年第9期13卷 1552-1560页

作者： Kuai Zhou Hai-Yuan Yang Peng-Yu Tang Wei Liu Yong-Jun Luo Bin Lv Jian Yin Tao Jiang Jian Chen Wei-Hua Cai Jin Fan Department of Orthopedics First Affiliated Hospital of Nanjing Medical University Department of Orthopedics Ben Q Hospital Affiliated to Nanjing Medical University Department of Orthopedics Affiliated Jiangning Hospital of Nanjing Medical University

Mitochondrial division inhibitor 1（Mdivi-1） is a selective cell-permeable inhibitor of dynamin-related protein-1（Drp1） and mitochondrial division.To investigate the effect of Mdivi-1 on cells treated with glutamate,cerebral cortex neurons isolated from neonatal rats were treated with 10 m M glutamate for 24 hours.Normal cultured cells and dimethyl sulfoxide-cultured cells were considered as controls.Apoptotic cells were detected by flow cytometry.Changes in mitochondrial morphology were examined by electron microscopy.Drp1,Bax,and casp ase-3 expression was evaluated by western blot assays and immunocytochemistry.Mitochondrial membrane potential was detected using the JC-1 probe.Twenty-four hours after 10 m M glutamate treatment,Drp1,Bax and caspase-3 expression was upregulated,Drp1 and Bax were translocated to mitochondria,mitochondrial membrane potential was decreased and the rate of apoptosis was increased.These effects were inhibited by treatment with 50 μM Mdivi-1 for 2 hours.This finding indicates that Mdivi-1 is a candidate neuroprotective drug that can potentially mitigate against neuronal injury caused by glutamate-induced excitotoxicity.

关键词： nerve regeneration mitochondrial division inhibitor 1 neurons apoptosis mitochondria division dynamin-related protein-I phospho-dynamin-related protein-1 Bax glutamate colocalization neural regeneration

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