CircRNA 001372 Reduces Inflammation in Propofol-Induced Neuroinflammation and Neural Apoptosis through PIK3CA/Akt/NF-κB by miRNA-148b-3p

Abstract

Objectives

To investigate effects of circular RNA (circRNA) 001372 and its antagonist miRNAs-148b-3p on propofol-induced neurotoxicity and neuroinflammation in rat brain and pheochromocytoma cells.

Methods

Sprague Dawley rats in propofol model group (n = 6) were intraperitoneal injected with propofol (50 mg/kg) and in sham control group (n = 6) without any treatment. Twenty-four h later, brain tissues were acquired during pentobarbital anesthesia. PC-12 cells were transfected with or without circRNA001372 mimics, circRNA001372 inhibitor, negative mimics or miRNA-148b-3p for 48 h and then treated with propofol (100 μM) for 48 h. Quantitative reverse transcription PCR and gene chips were used for detecting levels of circRNA001372, Haemotoxylin and Eosin staining for cell morphology, MTT for cell viability, flow cytometry for apoptosis, enzyme-linked immunosorbent assay for lactate dehydrogenase (LDH), interleukin-1β (IL-1β), IL-6, IL17 and IL-18, and Western blots for phosphoinositide 3-kinase (PI3K), Akt, phosphorylated Akt, and nuclear factor (NF) κB, dual-light luminescent reporter gene assay for luciferase reporter.

Results

The propofol anesthesia in rats decreases levels of circRNA001372 and increases levels of cytokines including IL-1β, IL-6, IL17 and IL-18, resulting in the neurocyte damage in brain. In propofol-treated PC-12 cells, the inhibition of circRNA001372 increases apoptosis and cell damage makers, including LDH, IL-1β, IL-6, IL17, IL-18, resulting in the reduction of cell viability, which have been revised after over-expression of circRNA001372. MiRNA-148b-3p reduces circRNA001372-incresed PI3K and pAKt levels but enhances the circRNA001372-decreased NFκB level.

Conclusions

CircRNA001372 suppresses propofol-induced neurotoxicity and neuroinflammation through PI3K/Akt/NF-κB signaling pathway in rat brain and neurocytes. MiRNA-148b-3p antagonizes the effects of circRNA001372.

Keywords:

• CircRNA 001372
• miRNA-148b-3p
• propofol
• neurotoxicity
• neuroinflammation
• PI3K/Akt

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was supported by the project of “Liaoning Clinical Research Center for Colorectal Cancer” (grant no. 2015225005); “Liaoning BaiQianWan Talents Program” [2017] No. C13; the National Natural Science Fund from the National Natural Science Foundation of China (grant nos. 81602407).