Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway
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
摘要：Mitochondrial division inhibitor 1 (Mdivi-1) is a selective cell-permeable inhibitor of dynamin-related protein-1 (Drp 1) 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 mM 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 mM 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.
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资助基金：This study was supported by the National Natural Science Foundation of China,(No.81371967 and 81401807)a grant from the 5th Phase of "Project 333" of Jiangsu Province of China,(No.BRA2016512)a grant from the Six Talent Peaks Project of Jiangsu Province of China,(No.2014-WSN-012)
论文发表日期：2018-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 1552-1560 )
英文信息