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Role of zinc dyshomeostasis in inflammasome formation in cultured cortical cells following lipopolysaccharide or oxygen-glucose deprivation/reperfusion exposure.
Neurobiology of Disease ( IF 6.1 ) Pub Date : 2020-01-23 , DOI: 10.1016/j.nbd.2020.104771
Hyun-Seo Park 1 , Min Heui Yoo 2 , Jae-Young Koh 3
Affiliation  

Exposure of mouse mixed cortical cell cultures to lipopolysaccharide (LPS) resulted in inflammasome formation in neurons and astrocytes, as indicated by increases in the levels of NLRP3, ASC, caspase-1, and IL-1β. LPS exposure concurrently increased the level of free zinc in the cytosol of both cell types. Addition of the membrane-permeant zinc chelator TPEN blocked the increases in the levels of NLRP3 and caspase-1 as well as the release of inflammatory cytokines, indicating a role for increased zinc in LPS-induced inflammasome formation. Oxygen-glucose deprivation (OGD), a cellular model of hypoxia, also induced inflammasome formation and zinc dyshomeostasis in cortical cells, effects that were abolished upon zinc chelation with TPEN. A similar mechanism appeared to be at work in vivo. Whereas intraperitoneal injection of LPS in mice resulted in inflammasome formation and microglial activation in the brain, it caused little induction of inflammasome formation in ZnT3-null mice, which lack synaptic zinc, suggesting a specific role for synaptic zinc in LPS-induced formation of inflammasomes in the mouse brain.

中文翻译:

在脂多糖或氧-葡萄糖剥夺/再灌注暴露后,锌运动异常在培养的皮质细胞中炎性体形成中的作用。

小鼠混合皮层细胞培养物暴露于脂多糖(LPS)会导致神经元和星形胶质细胞形成炎症小体,如NLRP3,ASC,caspase-1和IL-1β水平的升高所表明。暴露于LPS会同时增加两种细胞类型的细胞质中游离锌的水平。膜渗透性锌螯合剂TPEN的添加阻止了NLRP3和caspase-1水平的增加以及炎性细胞因子的释放,表明锌在LPS诱导的炎性体形成中的作用增加。缺氧的细胞模型氧葡萄糖剥夺(OGD)还可诱导皮质细胞中的炎症小体形成和锌异位稳态,而与TPEN螯合锌后这种作用被消除。类似的机制似乎在体内起作用。
更新日期:2020-01-24
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