Propofol induces oxidative stress and apoptosis in vitro via regulating miR‐363‐3p/CREB signalling axis

Abstract

Propofol, a generally used anaesthetic in patients care, has been proven to induce neurotoxicity. Studies have shown that miR-363-3p was closely related to neurological dysfunction, and the up-regulated miR-363-3p was recognized to be participate in propofol-induced neurotoxicity. However, the mechanisms and functions of miR-363-3p in propofol-induced neurotoxicity remain rarely reported. The aim of our research was to clarify the potential effects of miR-363-3p in neurotoxicity induced by propofol. SH-SY5Y cells were treated with propofol, miR-363-3p inhibitor or sh-CREB. quantitative real-time polymerase chain reaction and western blotting were applied to detect the expression of miR-363-3p, CREB, Bax, Bcl-2, cleaved caspase-9 and cleaved caspase-3 at the mRNA and/or protein level, respectively. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) in cell supernatant were detected using different kits. Flow cytometry and MTT assay were applied for assessing the functions of miR-363-3p and CREB on cell ability in cellular activity and apoptotic rate. In addition, Bioinformatic analysis and luciferase assay verified the relationship between 3 0-UTR of CREB and miR-363-3p. Our data indicated that the cell viability decreased with the increasing propofol concentration. Bioinformatic analysis and luciferase assay suggested that 3 0-UTR of transcript of CREB might be a binding site of miR-363-3p, and miR-363-3p could negatively regulate the expression of CREB. The changes in reactive oxygen species, LDH, SOD and MDA suggested that propofol mediates oxidative stress and apoptosis via modulating miR-363-3p/CREB axis. Propofol induces oxidative stress and apoptosis via affecting miR-363-3p/CREB axis in SH-SY5Y cells, suggesting miR-363-3p down-regulation may act as a novel strategy to ameliorate the propofol-induced neurotoxicity. Significance of the study: The present study demonstrated that propofol induces oxidative stress and apoptosis via affecting miR-363-3p/CREB axis in SH-SY5Y cells, suggesting miR-363-3p down-regulation may act as a novel strategy to ameliorate the propofol-induced neurotoxicity.

Hmgcs2 is the hub gene in diabetic cardiomyopathy and is negatively regulated by Hmgcs2, promoting high glucose‐induced cardiomyocyte injury

“…miR‐363 is a predictive, diagnostic, and prognostic biomarker for type 2 diabetes 47 . In addition, miR‐363 is able to suppress the pro‑inflammatory cytokine levels in cerebral ischemia/reperfusion injury 48 and moderate oxidative stress in the context of propofol‐induced neurotoxicity 49 . Our experimentation suggested miR‐363‐5p was downregulated in HG‐induced H9C2 cells and negatively regulated Hmgcs2, and miR‐363‐5p overexpression attenuated HG‐induced cell injury as evidenced by decreased LDH release, apoptosis, inflammation, and oxidative stress.…”

3-n-Butylphthalide suppresses neuroinflammation through BDNF signaling in postoperative cognitive dysfunction in mice

“…Impairment of antioxidant defense mechanisms like SOD is additionally a contributing element in the occurrence of oxidative harm. [43][44][45] Earlier investigations have demonstrated that NBP mitigates the deterioration of cognitive abilities induced by neuroin ammation through its inhibition in rats with diabetes. 35 Nevertheless, the previous studies have not provided a comprehensive explanation of the potential mechanisms through which NBP enhances postoperative cognitive dysfunction.…”

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

“…45 The expression of miR-363-3p and miR-34a in SH-SY5Y cells was dysregulated after propofol treatment, resulting in a decrease in the cell survival rate. 46,47 Propofol can cause neuronal injury during brain development by causing an imbalance of miRNA expression. 10,27,48 Zhu et al exposed hippocampal neurons of neonatal rats to 50 μM propofol for 6 h. PCR showed that after propofol treatment, the expression of miR-455-3p decreased and the expression of its target protein EphA4 increased, leading to a decrease in neuronal proliferation and an increase in apoptosis.…”

“…45 The expression of miR-363-3p and miR-34a in SH-SY5Y cells was dysregulated after propofol treatment, resulting in a decrease in the cell survival rate. 46,47 Propofol can cause neuronal injury during brain development by causing an imbalance of miRNA expression. 10,27,48 Zhu et al .…”