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Anti-inflammatory and anti-apoptotic effects of Zc3h12d against cerebral ischemia‒reperfusion through the modulation of the NF-κB signaling pathway
- Source :
- Brain Disorders, Vol 13, Iss , Pp 100115- (2024)
- Publication Year :
- 2024
- Publisher :
- Elsevier, 2024.
-
Abstract
- Objective: Anti-inflammatory and anti-apoptotic therapy is expected to become the focus for attenuating cerebral ischemia‒reperfusion injury (CIRI), but the underlying mechanism needs to be further elucidated. Zc3h12d has been reported to downregulate NF-κB signaling pathway. Nevertheless, no studies have been conducted to investigate whether Zc3h12d is associated with the development of CIRI. The aim of this study was to investigate whether Zc3h12d can ameliorate CIRI and the underlying mechanism. Methods: MCAO/R and OGD/R were performed to mimic CIRI in vitro and in vivo, respectively. The expression levels of Zc3h12d, proinflammatory cytokines, proapoptotic protein, and p-p65 were detected by RT‒qPCR, ELISA or Western blotting assays. Immunofluorescence staining was used to detect the spatial distribution of Zc3h12d and the expression of p-p65 in the nucleus. Apoptotic analyses were performed by TUNEL staining, Nissl staining and flow cytometry. Cell viability was assessed using the CCK-8 assay. Results: CIRI increased Zc3h12d expression and neuronal apoptosis in the brain. Zc3h12d was predominantly located in neurons in the cortex. Overexpression of Zc3h12d can inhibit inflammation and suppress neuronal apoptosis in cells after CIRI. Furthermore, overexpression of Zc3h12d decreased the expression of p-p65 in the nucleus, which was attenuated by TNF-α, a common NF-κB agonist. In addition, overexpression of Zc3h12d can also shorten the half-life of proinflammatory cytokines. Conclusion: Zc3h12d may play a crucial role in inhibiting inflammation and apoptosis after CIRI, and the underlying mechanism may be related to repressing the activation of NF-κB signaling. Targeting Zc3h12d may be a novel strategy for preventing CIRI.
Details
- Language :
- English
- ISSN :
- 26664593
- Volume :
- 13
- Issue :
- 100115-
- Database :
- Directory of Open Access Journals
- Journal :
- Brain Disorders
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.60de1df2bf04edab158334223db6e53
- Document Type :
- article
- Full Text :
- https://doi.org/10.1016/j.dscb.2023.100115