Jun-activated SOCS1 enhances ubiquitination and degradation of CCAAT/enhancer-binding protein β to ameliorate cerebral ischaemia/reperfusion injury.
C‐EBPβ
Jun
SOCS1
cerebral ischaemia/reperfusion injury
in vitro and in vivo studies
neuron apoptosis
neuroprotection
ubiquitination
Journal
The Journal of physiology
ISSN: 1469-7793
Titre abrégé: J Physiol
Pays: England
ID NLM: 0266262
Informations de publication
Date de publication:
28 Aug 2024
28 Aug 2024
Historique:
received:
10
09
2023
accepted:
18
06
2024
medline:
29
8
2024
pubmed:
29
8
2024
entrez:
28
8
2024
Statut:
aheadofprint
Résumé
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.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : the 2022 Jilin City Science and Technology Development Plan Project
ID : 202233126
Informations de copyright
© 2024 The Authors. The Journal of Physiology © 2024 The Physiological Society.
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