Jun‐activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer‐binding protein β to ameliorate cerebral ischaemia/reperfusion injury

Abstract

AbstractThis study investigates the molecular mechanisms behind ischaemia/reperfusion (I/R) injury in the brain, focusing on neuronal apoptosis. It scrutinizes the role of the Jun proto‐oncogene in apoptosis, involvement of SOCS1 in neural precursor cell accumulation in ischaemic regions, and the upregulation of C‐EBPβ in the hippocampus following I/R. Key to the study is understanding how Jun controls C‐EBPβ degradation via SOCS1, potentially offering new clinical treatment avenues for I/R. Techniques such as mRNA sequencing, KEGG enrichment analysis and protein–protein interaction (PPI) in mouse models have indicated involvement of Jun (AP‐1) in I/R‐induced cerebral damage. The study employs middle cerebral artery occlusion in different mouse models and oxygen–glucose deprivation/reoxygenation in cortical neurons to examine the impacts of Jun and SOCS1 manipulation on cerebral I/R injury and neuronal damage. The findings reveal that I/R reduces Jun expression in the brain, but its restoration lessens cerebral I/R injury and neuron death. Jun activates SOCS1 transcriptionally, leading to C‐EBPβ degradation, thereby diminishing cerebral I/R injury through the SOCS1/C‐EBPβ pathway. These insights provide a deeper understanding of post‐I/R cerebral injury mechanisms and suggest new therapeutic targets for cerebral I/R injury. imageKey points Jun and SOCS1 are poorly expressed, and C‐EBPβ is highly expressed in ischaemia/reperfusion mouse brain tissues. Jun transcriptionally activates SOCS1. SOCS1 promotes the ubiquitination‐dependent C‐EBPβ protein degradation. Jun blunts oxygen–glucose deprivation/reoxygenation‐induced neuron apoptosis and alleviates neuronal injury. This study provides a theoretical basis for the management of post‐I/R brain injury.