Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury
The spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and the mitochondrion is the most crucial interventional target. Rapamycin can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system. However, the impact of rapamycin via mod...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00865/full |
| _version_ | 1818418336944357376 |
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| author | Qiang Li Shane Gao Zhanrong Kang Meiyan Zhang Xin Zhao Yu Zhai Jianming Huang Guo-Yuan Yang Wanju Sun Jian Wang |
| author_facet | Qiang Li Shane Gao Zhanrong Kang Meiyan Zhang Xin Zhao Yu Zhai Jianming Huang Guo-Yuan Yang Wanju Sun Jian Wang |
| author_sort | Qiang Li |
| collection | DOAJ |
| description | The spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and the mitochondrion is the most crucial interventional target. Rapamycin can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system. However, the impact of rapamycin via modulating mitophagy and apoptosis after spinal cord ischemia-reperfusion injury remains unclear. This study was undertaken to investigate the potential role of rapamycin in modulating mitophagy and mitochondria-dependent apoptosis using the spinal cord ischemia-reperfusion injury (SCIRI) mouse model. We found that rapamycin significantly (p < 0.05) enhanced mitophagy by increasing the translocation of p62 and Parkin to the damaged mitochondria in the mouse spinal cord injury model. At the same time, rapamycin significantly (p < 0.05) decreased mitochondrial apoptosis related protein (Apaf-1, Caspase-3, Caspase-9) expression by inhibiting Bax translocation to the mitochondria and the release of the cytochrome c from the mitochondria. After 24 h following SCIRI, rapamycin treatment reduced the TUNEL+ cells in the spinal cord ischemic tissue and improved the locomotor function in these mice. Our results therefore demonstrate that rapamycin can improve the locomotor function by promoting mitophagy and attenuating SCIRI -induced apoptosis, indicating its potential therapeutic application in a spinal cord injury. |
| first_indexed | 2024-12-14T12:21:04Z |
| format | Article |
| id | doaj.art-c17a2706b6e84e35b8f7e0f205d7cd65 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-14T12:21:04Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-c17a2706b6e84e35b8f7e0f205d7cd652022-12-21T23:01:28ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-12-011210.3389/fnins.2018.00865415279Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion InjuryQiang Li0Shane Gao1Zhanrong Kang2Meiyan Zhang3Xin Zhao4Yu Zhai5Jianming Huang6Guo-Yuan Yang7Wanju Sun8Jian Wang9Department of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaEast Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaEast Hospital, Tongji University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Neurology, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaDepartment of Orthopedics, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai, ChinaNeuroscience and Neuroengineering Research Center, Med-X Research Institute and School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, ChinaDepartment of Orthopedics, Shanghai Pudong New Area People’s Hospital, Shanghai University of Medicine & Health Science, Shanghai, ChinaDepartment of Orthopedics, Shanghai Pudong New Area People’s Hospital, Shanghai University of Medicine & Health Science, Shanghai, ChinaThe spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and the mitochondrion is the most crucial interventional target. Rapamycin can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system. However, the impact of rapamycin via modulating mitophagy and apoptosis after spinal cord ischemia-reperfusion injury remains unclear. This study was undertaken to investigate the potential role of rapamycin in modulating mitophagy and mitochondria-dependent apoptosis using the spinal cord ischemia-reperfusion injury (SCIRI) mouse model. We found that rapamycin significantly (p < 0.05) enhanced mitophagy by increasing the translocation of p62 and Parkin to the damaged mitochondria in the mouse spinal cord injury model. At the same time, rapamycin significantly (p < 0.05) decreased mitochondrial apoptosis related protein (Apaf-1, Caspase-3, Caspase-9) expression by inhibiting Bax translocation to the mitochondria and the release of the cytochrome c from the mitochondria. After 24 h following SCIRI, rapamycin treatment reduced the TUNEL+ cells in the spinal cord ischemic tissue and improved the locomotor function in these mice. Our results therefore demonstrate that rapamycin can improve the locomotor function by promoting mitophagy and attenuating SCIRI -induced apoptosis, indicating its potential therapeutic application in a spinal cord injury.https://www.frontiersin.org/article/10.3389/fnins.2018.00865/fullapoptosismitophagyischemia-reperfusion injuryrapamycinspinal cord |
| spellingShingle | Qiang Li Shane Gao Zhanrong Kang Meiyan Zhang Xin Zhao Yu Zhai Jianming Huang Guo-Yuan Yang Wanju Sun Jian Wang Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury Frontiers in Neuroscience apoptosis mitophagy ischemia-reperfusion injury rapamycin spinal cord |
| title | Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury |
| title_full | Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury |
| title_fullStr | Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury |
| title_full_unstemmed | Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury |
| title_short | Rapamycin Enhances Mitophagy and Attenuates Apoptosis After Spinal Ischemia-Reperfusion Injury |
| title_sort | rapamycin enhances mitophagy and attenuates apoptosis after spinal ischemia reperfusion injury |
| topic | apoptosis mitophagy ischemia-reperfusion injury rapamycin spinal cord |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00865/full |
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