Propofol induces the apoptosis of neural stem cells via microRNA-9-5p / chemokine CXC receptor 4 signaling pathway

Abstract

Recent studies suggested that propofol, one of the most widely used anesthetics, may cause neurotoxicity in the developing brain, leading to cognitive deficits in adults. However, the underlying mechanisms remain unclear. In this study, we aimed to evaluate the mechanisms of propofol neurotoxicity in the neural stem cells (NSCs). The mRNA and protein expression levels of microRNA-9-5p (miR-9-5p) and chemokine CXC receptor 4 (CXCR4) were determined by quantitative reverse transcription-polymerase chain reaction and Western blotting analyses. Cell viability and apoptosis were evaluated using the cell counting kit-8 and Hoechst staining kits. The levels of apoptosis-related proteins B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein, and caspase-3 were detected by Western blotting analysis. These results confirmed that propofol activated cell apoptosis in a dose-dependent manner. A significant increase in the miR-9-5p and CXCR4 expression was observed in the propofol-treated cells. The overexpression of miR-9-5p induced apoptosis in NSCs, accompanied by elevated apoptosis-related protein activity. Furthermore, mitigated CXCR4 expression reduced propofol-induced cell apoptosis. We conclude that propofol induces cell death in NSCs, and overexpression of miR-9-5p/CXCR4 contributes to propofol-induced cell apoptosis, which might be a target for developing novel strategies to treat propofol neurotoxicity.

Recent progress on the role of non-coding RNA in postoperative cognitive dysfunction

“…Jiang et al, 2019). Recently, an increasing number of microRNA molecules [miR-21 (Twaroski et al, 2014), miR-206 (Li et al, 2017), miR-34a (Li et al, 2018), miR-215 (Tang et al, 2020), miR-363-3p (Yao and Zhang, 2020), miR-455-3p (Zhu et al, 2020), miR-9-5p (Zhang et al, 2022), and miR-582-5p (Zhang et al, 2020b)] have been revealed to be associated with propofol-induced neuronal apoptosis.…”

“…Historically, miR-665 in anesthesia-induced neurotoxicity was believed to directly down-regulate anti-apoptotic gene Bcl-2l1 expression, increasing caspase-3-mediated apoptosis rates ( Sun and Pei, 2015 , 2016 ; Sun et al, 2015 ; Jiang et al, 2019 ). Recently, an increasing number of microRNA molecules [miR-21 ( Twaroski et al, 2014 ), miR-206 ( Li et al, 2017 ), miR-34a ( Li et al, 2018 ), miR-215 ( Tang et al, 2020 ), miR-363-3p ( Yao and Zhang, 2020 ), miR-455-3p ( Zhu et al, 2020 ), miR-9-5p ( Zhang et al, 2022 ), and miR-582-5p ( Zhang et al, 2020b )] have been revealed to be associated with propofol-induced neuronal apoptosis. Meanwhile, the relationship between several microRNA types [miR-124 ( Yang et al, 2019 ), miR-153 ( Shao et al, 2019 ), miR-106a ( Zhang et al, 2020a ), and miR-142-5p ( Xie et al, 2020 )] and isoflurane-induced neuronal apoptosis has been demonstrated.…”

Role of ferroptosis in hypoxic preconditioning to reduce propofol neurotoxicity

“…Previous studies have shown that propofol reduces the oxygen metabolism rate of the brain, which has a brain-protective effect ( Engelhard et al, 2004 ; Wei et al, 2012 ; Wang et al, 2016 ; Zhang et al, 2016 ). However, in recent years, an increasing number of studies have shown that propofol is neurotoxic ( Shibuta et al, 2022 ; Zhang et al, 2022 ), induces central neurotoxicity in developing animals and may lead to long-term learning and cognitive dysfunction ( Chen et al, 2016 ; Li et al, 2019 ; Zhou et al, 2021 ). Our previous animal and cell experiments have shown that propofol has neurotoxicity, which not only leads to synaptic plasticity changes, decreased viability of hippocampal nerve cells, decreased survival rate of hippocampal nerve cells and increased apoptosis but also leads to abnormal development of neural networks.…”

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. ,,,− …”