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Journal of Translational Medicine

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Open Access 01-12-2020 | Shock | Research

HSP90 inhibitor 17AAG attenuates sevoflurane-induced neurotoxicity in rats and human neuroglioma cells via induction of HSP70

Authors: Min Liu, Moyun Li, Yu Zhou, Qian Zhou, Yugang Jiang

Published in: Journal of Translational Medicine | Issue 1/2020

Abstract

Background

17AAG has been extensively studied for its antitumor effects that protect cells from lethal stress by maintaining protein stability. The role of 17AAG in sevoflurane-induced neuronal injury has never been studied. We aim to investigate the effect of 17AAG on sevoflurane-induced neurotoxicity in vivo and in vitro.

Methods

Sevoflurane-induced hippocampal neuron injury model was established in aged Sprague–Dawley rats. Pretreatment of vehicle or 17AAG was administered prior to sevoflurane inhalation. H4 neuroglioma cells were pretreated with vehicle or 17AAG and exposed to sevoflurane. Apoptosis, oxidative stress, expression of interleukin-6 (IL-6), and activation of the nuclear factor-κB (NF-κB) signaling pathway in H4 cells were examined by Hoechst assay, flow cytometry, Western blot, and immunofluorescent staining. RNA interference against HSPA1A was performed to test the function of HSP70 in neuroprotection.

Results

Exogenous 17AAG reduced sevoflurane-induced apoptosis and oxidative stress in rat hippocampal neurons and in H4 cells. In H4 cells, 17AAG suppressed sevoflurane-induced upregulation of IL-6 and activation of NF-κB signaling. 17AAG enhanced sevoflurane-induced upregulation of HSP70 in rat hippocampal neurons and in H4 cells. Conversely, silencing of HSPA1A in H4 cells blocked the cytoprotective effect of 17AAG against sevoflurane-induced apoptosis and oxidative stress, and prevented upregulation of IL-6 and activation of NF-κB signaling.

Conclusions

17AAG protects against sevoflurane-induced neurotoxicity in vivo and in vitro via HSP70-dependent inhibition of apoptosis, oxidative stress, and pro-inflammatory signaling pathway.

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Title: HSP90 inhibitor 17AAG attenuates sevoflurane-induced neurotoxicity in rats and human neuroglioma cells via induction of HSP70
Authors: Min Liu
Moyun Li
Yu Zhou
Qian Zhou
Yugang Jiang
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Shock
Shock
Sevoflurane
Published in: Journal of Translational Medicine / Issue 1/2020
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-020-02332-w

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