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Journal of Molecular Neuroscience

, Volume 67, Issue 4, pp 622–631 | Cite as

Inhibition of BECN1 Suppresses Lipid Peroxidation by Increasing System Xc Activity in Early Brain Injury after Subarachnoid Hemorrhage

  • Yazhou GuoEmail author
  • Xiao Liu
  • Dezhong Liu
  • Kai Li
  • Changwei Wang
  • Yu Liu
  • Bing He
  • Pengfei Shi
Article

Abstract

Lipid peroxidation plays a crucial role in early brain injury (EBI) after subarachnoid hemorrhage (SAH), and cystine/glutamate antiporter system Xc has been proved to be associated with glutathione (GSH) synthesis, which protects cells against oxidative damage. Antioxidant effect of system Xc is mediated by Beclin 1 (BECN1). Therefore, this study aimed to determine whether administration of BECN1 small interfering RNA (siRNA) could attenuate EBI after SAH experiment, specifically through suppressing lipid peroxidation and increasing system Xc activity. Endovascular perforation was performed to induce SAH in a rat model and BECN1 siRNA was administered through intracerebroventricular injection. Neurological score, brain edema, lipid peroxidation (malondialdehyde, MDA), and antioxidation system, containing GSH, glutathione peroxidase (GSH-Px), glutathione reductase (GR), and anti-reactive oxygen species (anti-ROS), were examined. The expression of BECN1 and light chain of system Xc (xCT) was detected by western blot, immunoprecipitation, and immunofluorescence staining. This study confirmed that SAH induced neurological deficits and brain edema, which was accompanied by the increase of BECN1 expression and lipid peroxidation, and the decrease of xCT expression and antioxidative capacity. However, downregulation of BECN1 by siRNA could decrease the formation of the BECN1–xCT complex and lipid peroxidation, enhance antioxidative capacity, and ameliorate neurological deficits and brain edema in SAH rats. The results suggested that inhibition of BECN1 suppresses accumulation of lipid peroxidation by increasing system Xc activity in EBI after SAH, and BECN1 may be a new effective target for EBI treatment after SAH.

Keywords

Subarachnoid hemorrhage Early brain injury Lipid peroxidation BECN1 System Xc 

Notes

Compliance with Ethical Standards

Ethical Approval

All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

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Copyright information

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

Authors and Affiliations

  1. 1.Department of NeurosurgeryZhoukou Central HospitalZhoukou CityChina

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