Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury

Xiao,Bing; Chai,Yi; Lv,Shigang; Ye,Minhua; Wu,Miaojing; Xie,Liyuan; Fan,Yanghua; Zhu,Xingen; Gao,Ziyun

doi:10.3892/ijmm.2017.3106

Endothelial cell-derived exosomes protect SH-SY5Y nerve cells against ischemia/reperfusion injury

Authors:
- Bing Xiao
- Yi Chai
- Shigang Lv
- Minhua Ye
- Miaojing Wu
- Liyuan Xie
- Yanghua Fan
- Xingen Zhu
- Ziyun Gao
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Affiliations: Department of Neurosurgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China
Published online on: August 23, 2017 https://doi.org/10.3892/ijmm.2017.3106
Pages: 1201-1209
Copyright: © Xiao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cerebral ischemia is a leading cause of death and disability. A previous study indicated that remote ischemic postconditioning (RIP) in the treatment of cerebral ischemia reduces ischemia/reperfusion (I/R) injury. However, the underlying mechanism is not well understood. In the present study, the authors hypothesized that the protective effect of RIP on neurological damage is mediated by exosomes that are released by endothelial cells in femoral arteries. To test this, right middle cerebral artery occlusion/reperfusion with RIP was performed in rats. In addition, an I/R injury cell model was tested that included human umbilical vein endothelial cells (HUVECs) and SH-SY5Y cells. Both the in vivo and in vitro models were examined for injury. Markers of exosomes (CD63, HSP70 and TSG101) were assessed by immunohistochemistry, western blot analysis and flow cytometry. Exosomes were extracted from both animal serum and HUVEC culture medium and identified by electron microscopy. They investigated the role of endothelial cell-derived exosomes in the proliferation, apoptosis, cell cycle, migration and invasion of I/R-injured SH-SY5Y cells. In addition, apoptosis-related molecules caspase-3, Bax and Bcl-2 were detected. RIP was determined to increase the number of exosomes and the expression levels of CD63, HSP70 and TSG101 in plasma, but not in brain hippocampal tissue. The size of exosomes released after I/R in HUVECs was similar to the size of exosomes released in rats subjected to RIP. Endothelial cell-derived exosomes partly suppressed the I/R-induced cell cycle arrest and apoptosis, and inhibited cell proliferation, migration and invasion in SH-SY5Y nerve cells. Endothelial cell-derived exosomes directly protect nerve cells against I/R injury, and are responsible for the protective role of RIP in I/R.

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