Title:Sevoflurane Post-treatment Mitigates Oxygen-glucose Deprivationinduced
Pyroptosis of Hippocampal Neurons by Regulating the
Mafb/DUSP14 Axis
Volume: 19
Issue: 3
Author(s): Chen Chen*, Jianwei Zuo and Huimei Zhang
Affiliation:
- Department of Anesthesiology, Peking University Shenzhen Hospital, 1120 Lianhua Road, Shenzhen, Guangdong 518036, P.R. China
Keywords:
Sevoflurane post-treatment, Mafb, DUSP14, OGD, hippocampal neurons, pyroptosis, transcription factor, chromatin immunoprecipitation.
Abstract:
Background: Ischemic brain injury often results in irreversible pyroptosis of neurons.
Sevoflurane (Sevo) post-treatment exerts an alleviative role in neuroinflammation.
Objectives: This work evaluated the mechanism of Sevo post-treatment in oxygen-glucose deprivation
(OGD)-induced pyroptosis of rat hippocampal neurons.
Methods: Rat hippocampal neuron cell line H19-7 cells were treated with OGD, followed by posttreatment
of 2% Sevo. The expression patterns of Mafb ZIP Transcription Factor B (Mafb) and dual-
specificity phosphatase 14 (DUSP14) were determined via quantitative real-time polymerase
chain reaction (qRT-PCR) and Western blotting methods. H19-7 cell viability and the release of
lactate dehydrogenase (LDH) were examined via the cell counting kit-8 and LDH assay kits. Levels
of pyroptosis-related proteins and cytokines NOD-like receptor family, pyrin domain containing 3
(NLRP3), N-term cleaved Gasdermin-D (GSDMD-N), cleaved-caspase-1, interleukin (IL)-1β, and
IL-18 were also examined. The binding relation between Mafb and the DUSP14 promoter was detected.
Besides, the roles of Mafb/DUSP14 in OGD-induced pyroptosis of rat hippocampal neurons
were investigated through functional rescue experiments.
Results: Mafb and DUSP14 expression levels were decreased in OGD-induced hippocampal neurons.
Sevo post-treatment up-regulated Mafb and DUSP14, facilitated H19-7 cell viability, inhibited
LDH release, and reduced levels of NLRP3, GSDMD-N, cleaved-caspase-1, IL-1β, and IL-18. Mafb
increased DUSP14 expression via binding to the DUSP14 promoter. Repressing Mafb or DUSP14
exacerbated pyroptosis of hippocampal neurons.
Conclusion: Sevo post-treatment increased Mafb and DUSP14 expressions, which repressed OGDinduced
pyroptosis of hippocampal neurons.