Microglial and Neuronal Cell Pyroptosis Induced by Oxygen–Glucose Deprivation/Reoxygenation Aggravates Cell Injury via Activation of the Caspase-1/GSDMD Signaling Pathway

被引:0
作者
Zhaofei Dong
Qingxia Peng
Kuang Pan
Weijye Lin
Yidong Wang
机构
[1] Sun Yat-Sen University,Departments of Neurology, Sun Yat
[2] Sun Yat-Sen University,Sen Memorial Hospital
[3] Sun Yat-Sen University,The Eighth Affiliated Hospital
[4] Sun Yat-Sen University,Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of Medicine
来源
Neurochemical Research | 2023年 / 48卷
关键词
Pyroptosis; Neuron; Microglia; Inflammation; GasderminD (GSDMD); Necrosulfonamide;
D O I
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中图分类号
学科分类号
摘要
Pyroptosis is a new type of programmed cell death, which induces a strong pro-inflammatory reaction. However, the mechanism of pyroptosis after brain ischemia/reperfusion (I/R) and the interaction between different neural cell types are still unclear. This study comprehensively explored the mechanisms and interactions of microglial and neuronal pyroptosisin the simulated I/R environment in vitro. The BV2 (as microglial) and HT22(as neuronal) cells were treated by oxygen–glucose deprivation/reoxygenation (OGD/R). Both BV2 and HT22 cells underwent pyroptosis after OGD/R, and the pyroptosis occurred at earlier time point in HT22than that of BV2. Caspase-11 and Gasdermin E expression in BV2 and HT22 cells did not change significantly after OGD/R. Inhibition of caspase-1 or GSDMD activity, or down-regulation of GSDMD expression, alleviated pyroptosis in both BV2 and HT22 cells after OGD/R. Transwell studies further showed that OGD/R-treated HT22 or BV2 cells aggravated pyroptosis of adjacent non-OGD/R-treated cells, which could be relieved by inhibition of caspase-1 or GSDMD. These results suggested that OGD/R induces pyroptosis of microglia and neuronal cells and aggravates cell injury via activation of caspase-1/GSDMD signaling pathway. Our findings indicated that caspase-1 and GSDMD may be therapeutic targets after cerebral I/R.
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页码:2660 / 2673
页数:13
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