Background: The suppressor of cytokine signaling 3 (SOCS3) is a specific negative regulator of signal transducer and activator of transcription 3 (STAT3) signaling, which is predominantly activated to induce neuroinflammatory response in microglia and functions essential roles during cerebral ischemia-reperfusion (I/R) injury. Constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is a signaling platform controlling protein stability by remodeling of cullin-RING ubiquitin ligases, which is recently reported to specifically recognize proteins with SOCS-box domains. However, whether SOCS3 is related to COP9 signalosome in neuroinflammation during cerebral I/R injury is completely unclear.
Methods: Mice subjected to transient middle cerebral artery occlusion (MCAO) and reperfusion, and BV2 microglia cells treated with oxygen-glucose deprivation and reoxygenation (OGD/R) were used to mimic cerebral I/R injury. Western blot, qRTPCR, immunofluorescence, and co-Immunoprecipitation assays were performed to explore the regulatory mechanism of SOCS3 on neuroinflammation and the relationship of SOCS3 and COP9 signalosome during cerebral I/R injury.
Results: SOCS3 expression is significantly upregulated in microglia during OGD/R treatment, and overexpression of SOCS3 suppresses OGD/R-induced STAT3 activation and inflammatory factor expression. Furthermore, we find that COP9 signalosome subunit 3 (CSN3) interacts with SOCS3 protein to enhance its stability, thereby resulting in restricting OGD/R-induced STAT3 activation and inflammatory response. Moreover, we find that knockdown of CSN3 evidently accelerates STAT3 activation, and aggravates cerebral I/R injury in vivo.
Conclusion: CSN3 restricts neuroinflammatory responses during cerebral I/R injury through stabilizing SOCS3 protein and indicates that CSN3 a potential therapeutic target for cerebral I/R injury.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8075360 | PMC |
| http://dx.doi.org/10.2147/NDT.S298966 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Oxyglutamate Carrier Alleviates Cerebral Ischaemia-Reperfusion Injury by Regulating Mitochondrial Function.
Eur J Neurosci
January 2025
Department of Interventional Radiology, The Affiliated Hospital of Qingdao University, Qingdao, China.
Mitochondrial dysfunction has been reported to participate in the pathophysiological processes of cerebral ischaemia-reperfusion injury, which include reduced energy homeostasis, increased generation of oxidative stress species (ROS) and the release of apoptotic factors. Oxyglutamate carrier (OGC) is an important carrier protein on the inner mitochondrial membrane that can transport metabolites from the cytoplasm to the mitochondria. The role of OGC in cerebral ischaemia-reperfusion injury (I/R) remains unknown.
View Article and Find Full Text PDFL. protects cerebral ischemia/reperfusion injury via arachidonic acid/p53-mediated apoptosis axis.
Front Pharmacol
December 2024
State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
Introduction: Stroke is a debilitating disease and the second leading cause of death worldwide, of which ischemic stroke is the dominant type. L., also known as safflower, has been used to treat cerebrovascular diseases, especially ischemic stroke in many Asian countries.
View Article and Find Full Text PDFEffects of Cerium Oxide on Kidney and Liver Tissue Damage in an Experimental Myocardial Ischemia-Reperfusion Model of Distant Organ Damage.
Medicina (Kaunas)
December 2024
Department Cardiovascular Surgery, Gazi University Faculty of Medicine, Ankara 06560, Turkey.
Ischemia-reperfusion (I/R) injury is a process in which impaired perfusion is restored by restoring blood flow and tissue recirculation. Nanomedicine uses cutting-edge technologies that emerge from interdisciplinary influences. In the literature, there are very few in vivo and in vitro studies on how cerium oxide (CeO) affects systemic anti-inflammatory response and inflammation.
View Article and Find Full Text PDFHistone Deacetylase Inhibitors as a Promising Treatment Against Myocardial Infarction: A Systematic Review.
J Clin Med
December 2024
Department of Physiology, Universitat de Valencia, 46010 Valencia, Spain.
Acute myocardial infarction (AMI) is a critical medical condition that requires immediate attention to minimise heart damage and improve survival rates. Early identification and prompt treatment are essential to save the patient's life. Currently, the treatment strategy focuses on restoring blood flow to the myocardium as quickly as possible.
View Article and Find Full Text PDFmiRNA Expression: I/R Cardiomyocyte and Sevoflurane.
Biomolecules
December 2024
Department of Anesthesiology, Virgen de la Victoria University Hospital, 29010 Malaga, Spain.
Background: The effects of anesthetic drugs on myocardial cells have been a subject of research for the last 50 years. The clinical benefits of halogenated agents, particularly sevoflurane, have been demonstrated in cardiac surgery patients. These benefits are due to the action of different enzymes and a variety of molecular pathways mediated by the action of small noncoding RNAs (sRNA) such as microRNAs (miRNAs).
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!