Anti-microRNA-132 causes sevoflurane-induced neuronal apoptosis via the PI3K/AKT/FOXO3a pathway

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Abstract

In the present study, the mechanisms underlying the protective effects of microRNA-132 (miRNA-132) on sevoflurane-induced neuronal apoptosis were investigated. Reverse transcription-quantitative polymerase chain reaction and gene microarray hybridization were used to analyze alterations in microRNA levels. Cell viability, apoptosis and caspase-3/9 activity were measured using MTT, flow cytometry and caspase-3/9 activity kits. Immunofluorescence staining and western blot analysis were used to measure protein expression of phosphoinositide 3-kinase (PI3K) and phosphorylated (p-)AKT, forkhead box O3a (FOXO3a). In sevoflurane-induced rats, the expression of miRNA-132 was downregulated, compared with that in negative control rats. The downregulation of miRNA-132 increased neuronal apoptosis and the upregulation of miRNA-132 inhibited neuronal apoptosis in the sevoflurane-induced in vitro model. The downregulation of miRNA-132 suppressed the protein expression of PI3K and p-AKT, and suppressed the protein expression of FOXO3a in the sevoflurane-induced in vitro model. The PI3K inhibitor increased the effects of anti-miRNA-132 on neuronal apoptosis through the AKT/FOXO3a pathway in the sevoflurane-induced in vitro model. The promotion of FOXO3a inhibited the effects of anti-miRNA-132 on neuronal apoptosis through the AKT/FOXO3a pathway in the sevoflurane-induced in vitro model. These data suggested that miRNA-132 caused sevoflurane-induced neuronal apoptosis via suppression of the PI3K/AKT/FOXO3a pathway.

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Dicer and microRNAs protect adult dopamine neurons

Piotr Chmielarz, Julia Konovalova, Syeda Najam … (2017)

MicroRNAs (miRs) are important post-transcriptional regulators of gene expression implicated in neuronal development, differentiation, aging and neurodegenerative diseases, including Parkinson’s disease (PD). Several miRs have been linked to PD-associated genes, apoptosis and stress response pathways, suggesting that deregulation of miRs may contribute to the development of the neurodegenerative phenotype. Here, we investigate the cell-autonomous role of miR processing RNAse Dicer in the functional maintenance of adult dopamine (DA) neurons. We demonstrate a reduction of Dicer in the ventral midbrain and altered miR expression profiles in laser-microdissected DA neurons of aged mice. Using a mouse line expressing tamoxifen-inducible CreERT2 recombinase under control of the DA transporter promoter, we show that a tissue-specific conditional ablation of Dicer in DA neurons of adult mice led to decreased levels of striatal DA and its metabolites without a reduction in neuronal body numbers in hemizygous mice (DicerHET) and to progressive loss of DA neurons with severe locomotor deficits in nullizygous mice (DicerCKO). Moreover, we show that pharmacological stimulation of miR biosynthesis promoted survival of cultured DA neurons and reduced their vulnerability to thapsigargin-induced endoplasmic reticulum stress. Our data demonstrate that Dicer is crucial for maintenance of adult DA neurons, whereas a stimulation of miR production can promote neuronal survival, which may have direct implications for PD treatment.

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Inhibition of Autophagy via Activation of PI3K/Akt Pathway Contributes to the Protection of Ginsenoside Rb1 against Neuronal Death Caused by Ischemic Insults

Tianfei Luo, Guiying Liu, Hongxi Ma … (2014)

Lethal autophagy is a pathway leading to neuronal death caused by transient global ischemia. In this study, we examined the effect of Ginsenoside Rb1 (GRb1) on ischemia/reperfusion-induced autophagic neuronal death and investigated the role of PI3K/Akt. Ischemic neuronal death in vitro was induced by using oxygen glucose deprivation (OGD) in SH-SY5Y cells, and transient global ischemia was produced by using two vessels occlusion in rats. Cellular viability of SH-SY5Y cells was assessed by MTT assay, and CA1 neuronal death was evaluated by Hematoxylin-eosin staining. Autophagic vacuoles were detected by using both fluorescent microscopy in combination with acridine orange (AO) and Monodansylcadaverine (MDC) staining and transmission electronic microscopy. Protein levels of LC3II, Beclin1, total Akt and phosphor-Akt at Ser473 were examined by western blotting analysis. GRb1 inhibited both OGD and transient ischemia-induced neuronal death and mitigated OGD-induced autophagic vacuoles in SH-SY5Y cells. By contrast, PI3K inhibitor LY294002 counteracted the protection of GRb1 against neuronal death caused by either OGD or transient ischemia. LY294002 not only mitigated the up-regulated protein level of phosphor Akt at Ser473 caused by GRb1, but also reversed the inhibitory effect of GRb1 on OGD and transient ischemia-induced elevation in protein levels of LC3II and Beclin1.

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Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death.

Guoqi Zhu, Xuncui Wang, Shengbing Wu … (2012)

In an attempt to clarify the protective effect of puerarin on toxin-insulted dopaminergic neuronal death, this present study was carried out by using a typical Parkinson's disease (PD) model - 1-methyl-4-phenylpyridinium iodide (MPP(+))-induced dopaminergic SH-SY5Y cellular model. Data are presented, which showed that puerarin up-regulated Akt phosphorylation in both of MPP(+)-treated and non-MPP(+)-treated cells. The presence of PI3K inhibitor LY294002 completely blocked puerarin-induced activation of Akt phosphorylation. Moreover, puerarin decreased MPP(+)-induced cell death, which was blocked by phosphoinositide 3-kinase (PI3K) inhibitor LY294002. We further demonstrated that puerarin protected against MPP(+)-induced p53 nuclear accumulation, Puma (p53-upregulated mediator of apoptosis) and Bax expression and caspase-3-dependent programmed cell death (PCD). This protection was blocked by applying a PI3K/Akt inhibitor. Additionally, it was Pifithrin-α, but not Pifithrin-μ, which blocked MPP(+)-induced Puma and Bax expression, caspase-3 activation and cell death. Collectively, these data suggest that the activation of PI3K/Akt pathway is involved in the protective effect of puerarin against MPP(+)-induced neuroblastoma SH-SY5Y cell death through inhibiting nuclear p53 accumulation and subsequently caspase-3-dependent PCD. Puerarin might be a potential therapeutic agent for PD. Copyright Â© 2012 Elsevier Ltd. All rights reserved.

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Author and article information

Journal

Journal ID (nlm-ta): Int J Mol Med

Journal ID (iso-abbrev): Int. J. Mol. Med

Journal ID (publisher-id): IJMM

Title: International Journal of Molecular Medicine

Publisher: D.A. Spandidos

ISSN (Print): 1107-3756

ISSN (Electronic): 1791-244X

Publication date (Print): December 2018

Publication date (Electronic): 25 September 2018

Publication date PMC-release: 25 September 2018

Volume: 42

Issue: 6

Pages: 3238-3246

Affiliations

[1 ]Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, Shandong 250012

[2 ]Department of Anesthesiology, The People's Hospital of Chiping, Chiping, Shandong 252100, P.R. China

Author notes

Correspondence to: Ms. Bo Yang, Department of Anesthesiology, Qilu Hospital, Shandong University, 107 Wenhua West Road, Jinan, Shandong 250012, P.R. China, E-mail: bpy94861763@ 123456126.com

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Publisher ID: ijmm-42-06-3238

DOI: 10.3892/ijmm.2018.3895

PMC ID: 6202078

PubMed ID: 30272258

SO-VID: 30f50039-6b7e-4d38-b5e0-a810daef3c52

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This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Anti-microRNA-132 causes sevoflurane-induced neuronal apoptosis via the PI3K/AKT/FOXO3a pathway

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Neuronal Signaling

Most cited references 20

Dicer and microRNAs protect adult dopamine neurons

Inhibition of Autophagy via Activation of PI3K/Akt Pathway Contributes to the Protection of Ginsenoside Rb1 against Neuronal Death Caused by Ischemic Insults

Involvement of activation of PI3K/Akt pathway in the protective effects of puerarin against MPP+-induced human neuroblastoma SH-SY5Y cell death.

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