Inhibition of TRIM14 protects cerebral ischemia/reperfusion injury through regulating NF-κB/NLRP3 pathway-mediated inflammation and apoptosis.

Abstract

PURPOSE:

Many proteins in tripartite motif (TRIM) family have been reported to play an important role in cerebral ischemia/reperfusion (I/R) injury. This study was designed to investigate the effect of TRIM14 on the cerebral I/R injury in rats.

METHODS:

The rat model was constructed through inserting thread into the middle cerebral artery. The expression of TRIM14 was measured by qRT-PCR, immunoblotting, and immunofluorescence. The hippocampal sections were stained with 2,3,5-triphenyltetrazolium chloride (TTC) to determine infarct volume and used for measuring the neurologic deficit score and brain water content. The H&E staining was used for immunohistochemical (IHC) staining. The number of apoptotic cells was measured by fluorescence microscopy. The levels of IL-6, IL-1β, and TNFα were detected by qRT-PCR and ELISA. The swimming speed, latency time, and number of platform crossings were measured by the water maze test.

RESULTS:

TRIM14 was significantly enhanced in rats with cerebral I/R injury compared to Sham rats, showing its highest level at 24 h after I/R. TRIM14 inhibition reduced ischemic brain injury, suppressed neuron apoptosis, suppressed inflammation, and improved cognitive dysfunction in rats with cerebral I/R injury. TRIM14 inhibition also suppressed the activation of NF-κB/NLRP3 pathway in rats with cerebral I/R injury.

CONCLUSION:

In conclusion, the expression of TRIM14 was increased in rats with cerebral I/R injury, the protective effect of TRIM14 inhibitor on cerebral I/R injury in rats depends on its anti-apoptotic and anti-inflammatory effect. The underlying mechanism was, at least partially, through regulating NF-κB/NLRP3 pathway.

• Authors: Xianlong Xie, Fan Wang, Xiujuan Li
• Journal: Journal of receptor and signal transduction research (J Recept Signal Transduct Res) Vol. 42 Issue 2 Pg. 197-205 (Apr 2022) ISSN: 1532-4281 [Electronic] England
• PMID: 33691569 (Publication Type: Journal Article)

Chemical References

• NF-kappa B
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, rat
• Tripartite Motif Proteins

Topics

• Animals
• Apoptosis (genetics)
• Brain Ischemia (genetics, metabolism)
• Inflammation (genetics)
• NF-kappa B (metabolism)
• NLR Family, Pyrin Domain-Containing 3 Protein (genetics, metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (genetics, metabolism)
• Tripartite Motif Proteins (genetics, metabolism)