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The Neuroprotective Effect of miR-181a After Oxygen–Glucose Deprivation/Reperfusion and the Associated Mechanism

  • Xiangyu Liu
  • Lou Hong
  • Wenjuan Peng
  • Jun Jiang
  • Zhe Peng
  • Jianwen YangEmail author
Article
  • 24 Downloads

Abstract

The level of miR-181a decreases rapidly in N2a cells following oxygen–glucose deprivation/reperfusion, but its role in this process is unclear. Reelin, a regulator of neuronal migration and synaptogenesis, is a predicted target of miR-181a. We hypothesized that miR-181a reduces neuronal apoptosis and protects neurons by targeting reelin. Second mitochondria-derived activator of caspases (Smac) is a protein located in mitochondria that regulates apoptosis. The pro-apoptotic effect of Smac is achieved by reversing the effects of apoptosis-inhibiting proteins (IAPs), particularly X-linked inhibitor of apoptosis (XIAP). We also evaluated the effect of miR-181a on the Smac/IAP signaling pathway after oxygen–glucose deprivation and reperfusion in N2a cells. The miR-181a level, apoptosis rate, and the levels of reelin mRNA and protein, Smac, and XIAP were assessed in N2a cells subjected to oxygen–glucose deprivation for 4 h and reperfusion for 0, 4, 12, or 24 h with/without an miR-181a mimic, or mismatched control. Direct targeting of reelin by miR-181a was assessed in vitro by dual luciferase assay and immunoblotting. Pre-treatment with miR-181a mimicked the increase in the miR-181a level in N2a cells after oxygen–glucose deprivation/reperfusion, resulting in a significant decrease in the apoptosis rate. Changes in the miR-181a level in N2a cells were inversely correlated with reelin protein expression. Direct targeting of the reelin 3′ untranslated region by miR-181a was verified by dual luciferase assay, which showed that miR-181a significantly inhibited luciferase activity. The Smac level was significantly lower in the miR-181a mimics than the normal control and mimics-cont groups (P < 0.01), whereas the level of XIAP was increased slightly. These findings suggest that miR-181a protects neurons from apoptosis by inhibiting reelin expression and regulating the Smac/IAP signaling pathway after oxygen–glucose deprivation/reperfusion injury.

Keywords

Apoptosis miR-181a Oxygen–glucose deprivation reperfusion Reln Smac/IAP 

Notes

Funding Information

This study was supported by a grant from the Project of Health Department of Hunan Provincial Health Planning Commission (20180419).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Neurology, Hunan Provincial People’s HospitalNanhua UniversityChangshaChina
  2. 2.Department of Neurosurgery, The First Affiliated Hospital of Nanchang UniversityNanchang UniversityNanchangChina

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