MicroRNA-17-5p Protects against Propofol Anesthesia-Induced Neurotoxicity and Autophagy Impairment via Targeting BCL2L11

Abstract

Background. Propofol (PPF) has been shown in studies to cause cognitive impairment and neuronal cell death in developing animals. PPF has been demonstrated to decrease the expression of microRNA-17-5p (miR-17-5p) in a recent study. Nonetheless, the function of miR-17-5p in PPF-induced neurotoxicity and related mechanisms is uncharacterized. Methods. After the induction of neurotoxicity by treating the SH-SY5Y cells with PPF, qRT-PCR was conducted to evaluate the level of miR-17-5p. Using MTT and flow cytometry, cell viability and apoptosis rate were assessed, respectively. Interaction between miR-17-5p and BCL2 like 11 was (BCL2L11) studied using a Luciferase reporter assay. With the help of western blot analysis, we determined the level of proteins of apoptosis-related genes and autophagy-related markers. Results. In SH-SY5Y cells, PPF treatment induced neurotoxicity and downregulated miR-17-5p expression. In SH-SY5Y cells post-PPF exposure, overexpression of miR-17-5p increased cell viability and decreased apoptosis. Consistently, miR-17-5p mimics mitigated PPF-generated autophagy via inhibition of Atg5, Beclin1, and LC3II/I level and elevation of p62 protein expression. In addition, BCL2L11, which was highly expressed in PPF-treated SH-SY5Y cells, was directly targeted by miR-17-5p. Further, in PPF-treated SH-SY5Y cells, overexpressed BCL2L11 counteracted the suppressing behavior of miR-17-5p elevation on PPF-induced apoptosis. Conclusion. Overexpressed miR-17-5p alleviates PPF exposure-induced neurotoxicity and autophagy in SH-SY5Y cells via binding to BCL2L11, suggesting the possibility that miR-17-5p can serve as a candidate in the treatment of neurotoxicity (caused by PPF).

Anaesthesia and brain development: a review of propofol-induced neurotoxicity in pediatric populations

“…41 microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been found to be involved in the neurotoxicity process of propofol. 42,43 MicroRNAs (miRNAs) are endogenous noncoding RNA molecules with a length of approximately 22 nucleotides that regulate cellular processes by inhibiting the translation of messenger RNAs. 44 MiRNAs have become a research hotspot on the neurotoxicity of anesthetics in recent years.…”

“…41 microRNAs (miRNAs) and long noncoding RNAs (lncRNAs) have been found to be involved in the neurotoxicity process of propofol. 42,43…”

Propofol-Induced Developmental Neurotoxicity: From Mechanisms to Therapeutic Strategies

“…The genetic background of higher expression of LRCF can be used as a marker to identify high-risk patients with OLG damage caused by propofol . In addition, it is found that miR-665, miR-9-5p/CXC chemokine receptor 4 (CXCR4) axis, miR-455-3p/EPH receptor A4 (EphA4) axis, miR-363-3p/CREB axis, miR-215/large tumor suppressor homologue 2 (LATS2) axis, miR-34a/mitogen-activated protein kinase kinase (MEK)/ERK signaling pathway, miR-206/p53 upregulated modulator of apoptosis (PUMA) axis, miR-17-5p/Bcl-2-like protein 11 (BCL2L11) axis, and signal transducer and activator of transcription 3 (STAT3)/miR-21/Sprouty 2/Akt signaling pathway are all involved in propofol-induced neuronal apoptosis. ,,,− …”

Research progress on molecular mechanisms of general anesthetic-induced neurotoxicity and cognitive impairment in the developing brain

“…At present, great progress has been made in the treatment of neurotoxicity of general anesthetics by targeting miRNAs. Recent studies have shown that miR-17-5P can alleviate the neurotoxicity induced by propofol and isoflurane exposure ( 34 , 35 ), which may serve as a potential drug direction for future research and development of general anesthetic neurotoxicity. Similarly, Chen et al found that miR-384-3p can alleviate sevoflurane-induced apoptosis and morphological changes of hippocampal neurons, and also improve cognitive impairment, such as the sevoflurane-induced decline in learning and memory ability ( 36 ), which is of great help in relieving and treating cognitive impairment caused by general anesthesia and is a potential new therapeutic strategy.…”