UBE2H Inhibits Pyroptosis in Microglia Cells following Ischemic Stroke by Mediating the Ubiquitination of p53/CASP1

Abstract

Background: Ischemic stroke is the leading cause of permanent disability, affecting approximately 14 million people annually. Therefore, this study aimed to elucidate the role and underlying mechanism of p53/cysteinyl aspartate specific proteinase 1 (CASP1) in ischemic stroke. Methods: The raw data regarding ischemic stroke were acquired from the GSE97537 data set of Gene Expression Omnibus (GEO). Moreover, a mouse model of cerebral ischemia was established. Neurons and microglia cells were used for in vitro experiments. Quantitative polymerase chain reaction (qPCR) and western blot analysis were used to assess the expression levels of target genes. Results: We observed that ubiquitinconjugating enzyme E2H (UBE2H) expression was downregulated following ischemic stroke. The expression of UBE2H was found to promote pyroptosis of microglia cells. Furthermore, a negative correlation was observed between CASP1 and UBE2H. The inhibition of CASP1 significantly reduced pyroptosis, while the inhibition of UBE2H increased CASP1 activity in microglia. Additionally, we observed a close association between elevated CASP1 expression and poorer survival in ischemic stroke. Conclusions: In summary, this study indicates that UBE2H inhibits microglial apoptosis following ischemic stroke by mediating the ubiquitination of p53/CASP1.