Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway
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 mM gluta...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Medknow Publications
2018-01-01
|
| Series: | Neural Regeneration Research |
| Subjects: | |
| Online Access: | http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=9;spage=1552;epage=1560;aulast=Zhou |
| _version_ | 1819206759154188288 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Kuai Zhou |
| collection | DOAJ |
| description | 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 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 caspase-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. |
| first_indexed | 2024-12-23T05:12:42Z |
| format | Article |
| id | doaj.art-677a17df690c4fe2b633c7fd73a5d5cf |
| institution | Directory Open Access Journal |
| issn | 1673-5374 |
| language | English |
| last_indexed | 2024-12-23T05:12:42Z |
| publishDate | 2018-01-01 |
| publisher | Wolters Kluwer Medknow Publications |
| record_format | Article |
| series | Neural Regeneration Research |
| spelling | doaj.art-677a17df690c4fe2b633c7fd73a5d5cf2022-12-21T17:58:56ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742018-01-011391552156010.4103/1673-5374.235299Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathwayKuai ZhouHai-Yuan YangPeng-Yu TangWei LiuYong-Jun LuoBin LvJian YinTao JiangJian ChenWei-Hua CaiJin FanMitochondrial 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 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 caspase-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.http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=9;spage=1552;epage=1560;aulast=Zhounerve regeneration; mitochondrial division inhibitor 1; neurons; apoptosis; mitochondria; division; dynamin-related protein-1; phospho-dynamin-related protein-1; Bax; glutamate; colocalization; neural regeneration |
| spellingShingle | 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 Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway Neural Regeneration Research nerve regeneration; mitochondrial division inhibitor 1; neurons; apoptosis; mitochondria; division; dynamin-related protein-1; phospho-dynamin-related protein-1; Bax; glutamate; colocalization; neural regeneration |
| title | Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway |
| title_full | Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway |
| title_fullStr | Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway |
| title_full_unstemmed | Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway |
| title_short | Mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity: a mechanistic pathway |
| title_sort | mitochondrial division inhibitor 1 protects cortical neurons from excitotoxicity a mechanistic pathway |
| topic | nerve regeneration; mitochondrial division inhibitor 1; neurons; apoptosis; mitochondria; division; dynamin-related protein-1; phospho-dynamin-related protein-1; Bax; glutamate; colocalization; neural regeneration |
| url | http://www.nrronline.org/article.asp?issn=1673-5374;year=2018;volume=13;issue=9;spage=1552;epage=1560;aulast=Zhou |
| work_keys_str_mv | AT kuaizhou mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT haiyuanyang mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT pengyutang mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT weiliu mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT yongjunluo mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT binlv mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT jianyin mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT taojiang mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT jianchen mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT weihuacai mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway AT jinfan mitochondrialdivisioninhibitor1protectscorticalneuronsfromexcitotoxicityamechanisticpathway |