2. Academic Validation
  3. Jun-activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer-binding protein β to ameliorate cerebral ischaemia/reperfusion injury

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

  • J Physiol. 2024 Oct;602(19):4959-4985. doi: 10.1113/JP285673.
Chuan He 1,  Tie Wang 2,  Yanwu Han 3,  Changyang Zuo 4,  Guangming Wang 3
Affiliations

Affiliations

  • 1 Department of Gastroenterology, The First Hospital of Jilin University, Changchun, P.R. China.
  • 2 Department of Clinical Laboratory, The First Hospital of Jilin University, Changchun, P.R. China.
  • 3 Department of Neurosurgery, The First Hospital of Jilin University, Changchun, P.R. China.
  • 4 Department of Neurosurgery, Suzhou Ninth Hospital Affiliated to Soochow University, Suzhou, P.R. China.
PMID: 39197117 DOI: 10.1113/JP285673
Abstract

This 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. KEY 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.

Keywords

C‐EBPβ; Jun; SOCS1; cerebral ischaemia/reperfusion injury; in vitro and in vivo studies; neuron apoptosis; neuroprotection; ubiquitination.

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