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Front. Neurosci. | doi: 10.3389/fnins.2018.00865

Rapamycin enhances mitophagy and attenuates apoptosis after spinal ischemia-reperfusion injury

Qiang Li1, Zhanrong Kang2,  Shane Gao3, Meiyan Zhang3, Xin Zhao1, Yu Zhai1, Jianming Huang2,  Guoyuan Yang4, Wanju Sun5* and  Jian Wang5, 6*
  • 1Shanghai Ninth People’s Hospital, Shanghai Jiao-Tong University School of Medicine, China
  • 2Shanghai Pudong Hospital, China
  • 3Shanghai East Hospital, Tongji University School of Medicine, China
  • 4Med-X Research Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, China
  • 5Shanghai Pudong New Area People's Hospital, China
  • 6Shanghai Pudong New Area Public Interest Hospital, China

Spinal cord is extremely vulnerable to ischemia-reperfusion (I/R) injury, and 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 by 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 via increasing the translocation of p62 and Parkin to the damaged mitochondria in the mouse spinal cord injury model. Meanwhile, rapamycin significantly (p<0.05) decreased mitochondrial apoptosis related proteins (Apaf-1, Caspase-3, Caspase-9) expression via inhibiting Bax translocation to mitochondria and cytochrome c release from mitochondria . After 24 hours following SCIRI, rapamycin treatment apparently reduced TUNEL+ cells in spinal cord ischemic tissue and improved locomotor function in these mice. Thus, our results demonstrate that rapamycin can improve the locomotor function via promoting mitophagy and attenuating SCIRI -induced apoptosis, indicating its potential therapeutic application against spinal cord injury.

Keywords: Apoptosis, mitophagy, ischemia-reperfusion injury, rapamycin, Spinal Cord

Received: 22 Jul 2018; Accepted: 05 Nov 2018.

Edited by:

Gang Chen, First Affiliated Hospital of Soochow University, China

Reviewed by:

Xuping Li, Houston Methodist Research Institute, United States
Lezi E, Duke University, United States  

Copyright: © 2018 Li, Kang, Gao, Zhang, Zhao, Zhai, Huang, Yang, Sun and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence:
Prof. Wanju Sun, Shanghai Pudong New Area People's Hospital, Pudong, China, sunwanjudoctor@hotmail.com
Prof. Jian Wang, Shanghai Pudong New Area Public Interest Hospital, Pudong, China, purenyiwj@163.com