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Inhibition of PRMT5 attenuates cerebral ischemia/reperfusion–Induced inflammation and pyroptosis through suppression of NF–κB/NLRP3 axis.
- Source :
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Neuroscience Letters . Apr2022, Vol. 776, pN.PAG-N.PAG. 1p. - Publication Year :
- 2022
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Abstract
- • we have reported for the first time that PRMT5 expression was up-regulated in both cell and animal I/R models. • Inhibition of PRMT5 attenuates cerebral I/R–induced infammation and pyroptosis. • Rescue experiment proved that the pro-infammatory and pro-pyroptotic effect of PRMT5 was the consequence of activation of NF-κB/NLRP3 axis. Protein methylation is a prevalent post-translational modification after cerebral ischemia. Protein arginine methyltransferase 5 (PRMT5) is a type of methyltransferase enzyme that can catalyse the formation of methylated residues on histones and non-histone proteins. Accumulating evidence suggested that PRMT5 might play a carcinogenic role in various cancers. However, the role of PRMT5 in cerebral ischaemia/reperfusion (I/R) injury remains unclear. In this project, middle cerebral artery occlusion/reperfusion (MCAO/R) model in mice and oxygen-glucose deprivation/reoxygenation (OGD/R) model in human neuroblastoma SH-SY5Y cells were utilized to mimic disease state of cerebral I/R. We found that expression of inflammatory-related factors [Interleukin (IL)-1β and IL-6)] and pyroptotic-related factor [N-term cleaved Gasdermin-D (GSDMD-N)] were up-regulated in both MCAO/R mice and OGD/R SH-SY5Y cells. In addition, both in vivo and in vitro, PRMT5 was aberrantly upregulated during cerebral I/R. However, these alterations induced by I/R were blocked by PRMT5 inhibitor LLY-283, and enhanced by overexpression of PRMT5. Furthermore, rescue experiment proved that PRMT5 plays a pro-inflammatory and pro-pyroptotic role by activating nuclear factor kappa B (NF-κB)/nucleotide-binding oligomerization domainlike receptor pyrin domain containing 3 (NLRP3) axis. Finally, we observed that treatment of LLY-283 alleviated neurological deficits and reduced infarct volume in the MCAO/R mice. Taken together, PRMT5 may be a potential therapeutic target for cerebral I/R injury. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 03043940
- Volume :
- 776
- Database :
- Academic Search Index
- Journal :
- Neuroscience Letters
- Publication Type :
- Academic Journal
- Accession number :
- 155961442
- Full Text :
- https://doi.org/10.1016/j.neulet.2022.136576