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.
Keywords: Sevoflurane post-treatment, Mafb, DUSP14, OGD, hippocampal neurons, pyroptosis, transcription factor, chromatin immunoprecipitation.
[http://dx.doi.org/10.1016/j.amjmed.2021.07.027] [PMID: 34454905]
[http://dx.doi.org/10.3390/ijms21186454] [PMID: 32899616]
[http://dx.doi.org/10.3390/ijms19092834] [PMID: 30235837]
[http://dx.doi.org/10.1038/s41423-020-00630-3] [PMID: 33785842]
[http://dx.doi.org/10.1111/cpr.12563] [PMID: 30525268]
[http://dx.doi.org/10.1186/s12974-020-02040-8] [PMID: 33402173]
[http://dx.doi.org/10.3389/fphar.2020.590453] [PMID: 33424599]
[http://dx.doi.org/10.1186/s12974-020-01988-x] [PMID: 33153475]
[http://dx.doi.org/10.1007/s12630-020-01791-5] [PMID: 32812189]
[http://dx.doi.org/10.1016/j.bja.2021.01.033] [PMID: 33722372]
[http://dx.doi.org/10.1016/j.brainresbull.2018.05.020] [PMID: 29857124]
[http://dx.doi.org/10.3389/fcell.2021.658720] [PMID: 34422795]
[http://dx.doi.org/10.1016/j.ejphar.2019.01.051] [PMID: 30710551]
[http://dx.doi.org/10.1159/000503727] [PMID: 31655824]
[http://dx.doi.org/10.3389/fimmu.2020.603507] [PMID: 33312178]
[http://dx.doi.org/10.1007/s00125-015-3673-x] [PMID: 26115698]
[http://dx.doi.org/10.1038/s41598-019-45528-x] [PMID: 31235823]
[http://dx.doi.org/10.7554/eLife.54903] [PMID: 32452758]
[http://dx.doi.org/10.1155/2020/6458204] [PMID: 32090104]
[http://dx.doi.org/10.1016/j.pneurobio.2020.101906] [PMID: 32905807]
[PMID: 32633405]
[http://dx.doi.org/10.1038/nm.4312] [PMID: 28394332]
[http://dx.doi.org/10.4103/2045-9912.318860] [PMID: 34213497]
[http://dx.doi.org/10.1159/000445661] [PMID: 27448450]
[http://dx.doi.org/10.1093/nar/gkab1113] [PMID: 34850907] [http://dx.doi.org/10.1016/j.bbrc.2018.12.170] [PMID: 30638656]
[http://dx.doi.org/10.1016/j.bbadis.2018.09.012] [PMID: 31699365]
[http://dx.doi.org/10.3390/genes13010048] [PMID: 35052389]
[http://dx.doi.org/10.3390/ijms21197380] [PMID: 33036265]
[http://dx.doi.org/10.1007/s12975-020-00806-z] [PMID: 32219729]
[http://dx.doi.org/10.1186/s12871-018-0636-z] [PMID: 30447684]
[http://dx.doi.org/10.1080/21655979.2021.1947443] [PMID: 34227902]
[http://dx.doi.org/10.1155/2022/9030771] [PMID: 35178162]
[http://dx.doi.org/10.1111/cns.13715] [PMID: 34370899]
[http://dx.doi.org/10.12659/MSM.930042] [PMID: 34059615]
[http://dx.doi.org/10.1016/j.neuroscience.2017.05.004] [PMID: 28501505]
[http://dx.doi.org/10.1007/s12035-021-02402-0] [PMID: 33970453]
[http://dx.doi.org/10.1080/13813455.2020.1773860] [PMID: 32538180]
[http://dx.doi.org/10.1002/dneu.22859] [PMID: 34679244]
[http://dx.doi.org/10.1186/s12944-015-0078-2] [PMID: 26204962]
[http://dx.doi.org/10.1167/iovs.17-23319] [PMID: 29860460]