Propofol inhibited apoptosis of hippocampal neurons in status epilepticus through miR-15a-5p/NR2B/ERK1/2 pathway

Abstract

Although a previous study reported that propofol had a therapeutic effect in status epilepticus (SE), the mechanisms underlying the effect of propofol in SE remain unclear. The aim of this study was to explore the regulatory mechanisms underlying propofol-induced inhibition of SE.A rat SE model was established using the lithium-pilocarpine injection method. A qRT-PCR and Western blot were utilized to detect the expression of relative molecules. Cell apoptosis was evaluated by a flow cytometry assay. The interaction between miR-15a-5p and NR2B was assessed using a luciferase reporter assay.Propofol inhibited cell apoptosis and increased miR-15a-5p expression both in hippocampal tissues of SE rats and low Mg 2+ -induced hippocampal neurons. Propofol-induced attenuation of apoptosis of low Mg 2+ -induced hippocampal neurons was mediated by miR-15a-5p. miR-15a-5p targeted NR2B and negatively regulated its expression. Propofol downregulated NR2B expression, mediated by miR-15a-5p. In terms of the mechanism of action, propofol suppressed the apoptosis of Mg 2+ -induced hippocampal neurons through the miR-15a-5p/NR2B/ERK1/2 pathway. In vivo experiment suggested that propofol inhibited the apoptosis of hippocampal neurons in SE rats by upregulating miR-15a-5p.In terms of the molecular mechanism of propofol, it appears to inhibit apoptosis of hippocampal neurons in SE through the miR-15a-5p/NR2B/ERK1/2 pathway. The findings provide theoretical support for propofol treatment of SE.

RETRACTED ARTICLE: Propofol inhibits migration and induces apoptosis of pancreatic cancer PANC-1 cells through miR-34a-mediated E-cadherin and LOC285194 signals

“…Specifically, the following findings from cell culture models showed that miR-15a-5p [53], MicroRNA-582-5p [54] and miR-34a [55] were involved in propofol-induced neuron and astrocyte death, respectively; miR-21 was involved in propofol-induced inhibition of proliferation and epithelial-mesenchymal transition in breast cancer cells [56]; miR-495 was involved in propofol-induced inhibition of proliferation and metastasis in JEG-3 choriocarcinoma cells [57]. In this study, propofol treatment decreased cell migration followed by miR-34a and E-cadherin upregulation in the PANC-1 cells.…”

Roles of N-Methyl-D-Aspartate Receptors (NMDARs) in Epilepsy

“…MicroRNA-34c has also been found to play a negative role in seizure and cognitive function, possibly by regulating NMDARs and AMPARs associated with LTP (Huang et al, 2018). Both in hippocampal tissues of SE rats and low Mg-induced hippocampal neurons, propofol can inhibit apoptosis of hippocampal neurons by microRNA-15a-5p/GluN2B/ERK1/2 pathway, which provides theoretical support for propofol treatment of SE (Liu et al, 2020). MicroRNA-124 suppresses seizure and regulates CREB1 activity.…”

Non-Coding RNAs as Novel Regulators of Neuroinflammation in Alzheimer’s Disease

“…In addition, miR-15a upregulation induces the expression of autophagy-related proteins, indicating that miR-15a is involved in AKT3-mediated autophagy via AKT3 inhibition. Moreover, miR-15a-5P targets NR2B in epileptic patients, negatively regulating its expression and inhibiting neuronal apoptosis in the hippocampus ( 77 ). The specific mechanism of miR-15a’s action in AD is unclear and requires further study.…”