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HDAC3 deacetylates H3K27ac and H3K9ac on the TrkC promoter to exacerbate sevoflurane-induced neurotoxicity

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Molecular & Cellular Toxicology Aims and scope Submit manuscript

Abstract

Background

Sevoflurane (Sev) is a widely used general anesthetic that can cause neurotoxicity. Histone acetylation is a vital epigenetic mechanism responding to environmental stresses.

Objective

This study was conducted to analyze the role of histone deacetylase 3 (HDAC3) in Sev-induced neurotoxicity and provide a theoretical reference for the treatment of anesthetic neurotoxicity.

Results

HDAC3 was upregulated in Sev-treated HT-22 cells. Inhibition of HDAC3 upregulated cell viability and downregulated apoptosis, oxidative stress and secretion of inflammatory cytokines. HDAC3 reduced H3K27ac and H3K9ac levels on the TrkC promoter to inhibit TrkC expression. TrkC downregulation reversed the alleviative role of si-HDAC3 in Sev-induced neurotoxicity.

Conclusion

HDAC3 enhanced Sev-induced neurotoxicity by reducing H3K27ac and H3K9ac to repress TrkC.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgement

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Anesthesiology, People’s Hospital of Ganzhou, Ganzhou, 341000, China

    Jiegang Zhou & Dan Wang

  2. Department of Nursing, The Fifth People’s Hospital of Ganzhou, No. 666 Dongjiangyuan Avenue, Zhanggong District, Ganzhou, 341000, China

    Xinwei Feng

Authors
  1. Jiegang Zhou
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  2. Xinwei Feng
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  3. Dan Wang
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Contributions

Conceptualization: JZ, XF, Dan Wang; Methodology: JZ, XF; Data curation: JZ, XF, DW; Validation: JZ; Supervision: XF; Writing – original draft: JZ; Writing – review and editing: JZ, XF, DW.

Corresponding author

Correspondence to Xinwei Feng.

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Conflict of interest

Jiegang Zhou, Xinwei Feng and Dan Wang declare that there is no conflict of interest.

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Zhou, J., Feng, X. & Wang, D. HDAC3 deacetylates H3K27ac and H3K9ac on the TrkC promoter to exacerbate sevoflurane-induced neurotoxicity. Mol. Cell. Toxicol. (2023). https://doi.org/10.1007/s13273-023-00394-7

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  • DOI: https://doi.org/10.1007/s13273-023-00394-7

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