Propofol protects hippocampal neurons from apoptosis in ischemic brain injury by increasing GLT-1 expression and inhibiting the activation of NMDAR via the JNK/Akt signaling pathway

Gong,Hong-Yan; Zheng,Fang; Zhang,Chao; Chen,Xi-Yan; Liu,Jing-Jing; Yue,Xiu-Qin

doi:10.3892/ijmm.2016.2663

Propofol protects hippocampal neurons from apoptosis in ischemic brain injury by increasing GLT-1 expression and inhibiting the activation of NMDAR via the JNK/Akt signaling pathway

Authors:
- Hong-Yan Gong
- Fang Zheng
- Chao Zhang
- Xi-Yan Chen
- Jing-Jing Liu
- Xiu-Qin Yue
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Affiliations: Department of Anesthesia, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Ultrasound, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Orthopaedics, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China, Department of Emergency, The First Affiliated Hospital of Xinxiang Medical University, Weihui, Henan 453100, P.R. China
Published online on: July 5, 2016 https://doi.org/10.3892/ijmm.2016.2663
Pages: 943-950

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Abstract

Ischemic brain injury (IBI) can cause nerve injury and is a leading cause of morbidity and mortality worldwide. The neuroprotective effects of propofol against IBI have been previously demonstrated. However, the neuroprotective effects of propofol on hippocampal neurons are not yet entirely clear. In the present study, models of IBI were established in hypoxia-exposed hippocampal neuronal cells. Cell viability assay and apoptosis assay were performed to examine the neuroprotective effects of propofol on hippocampal neurons in IBI. A significant decrease in cell viability and a significant increase in cell apoptosis were observed in the IBI group compared with the control group, accompanied by a decrease in glial glutamate transporter-1 (GLT‑1) expression as determined by RT-qPCR and western blot analysis. The effects of IBI were reversed by propofol treatment. The siRNA-mediated knockdown of GLT‑1 in the hypoxia-exposed hippocampal neuronal cells led to an increase in cell apoptosis, Jun N-terminal kinase (JNK) activation and N-methyl-D‑aspartate (NMDA) receptor (NR1 and NR2B) activation, as well as to a decrease in cell viability and a decrease in Akt activation. The effects of RNA interference-mediated GLT‑1 gene silencing on cell viability, JNK activation, NMDAR activation, cell apoptosis and Akt activation in the hippocampal neuronal cells were slightly reversed by propofol treatment. The JNK agonist, anisomycin, and the Akt inhibitor, LY294002, both significantly blocked the effects of propofol on hippocampal neuronal cell viability and apoptosis in IBI. The decrease in JNK activation and the increase in Akt activation caused by GLT‑1 overexpression were reversed by NMDA. Collectively, our findings suggest that propofol treatment protects hippocampal neurons against IBI by enhancing GLT‑1 expression and inhibiting the activation of NMDAR via the JNK/Akt signaling pathway.

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