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Download fileEndoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis via Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells
journal contribution
posted on 2022-01-25, 13:06 authored by Jianzhao Liao, Zhuoying Hu, Quanwei Li, Hongji Li, Weijin Chen, Haihua Huo, Qingyue Han, Hui Zhang, Jianying Guo, Lianmei Hu, Jiaqiang Pan, Ying Li, Zhaoxin TangCopper
(Cu) is a common additive in food products, which poses
a potential concern to animal and human health when it is in excess.
Here, we investigated the relationship between endoplasmic reticulum
(ER) stress and pyroptosis in Cu-induced toxicity of jejunum in vivo and in vitro. In in vivo experiments, excess intake of dietary Cu caused ER cavity expansion,
elevated fluorescence signals of GRP78 and Caspase-1, and increased
the mRNA and protein expression levels related to ER stress and pyroptosis
in pig jejunal epithelium. Simultaneously, similar effects were observed
in IPEC-J2 cells under excess Cu treatment. Importantly, 4-phenylbutyric
acid (ER stress inhibitor) and MKC-3946 (IRE1α inhibitor) significantly
inhibited the ER stress-triggered IRE1α-XBP1 pathway, which
also alleviated the Cu-induced pyroptosis in IPEC-J2 cells. In general,
these results suggested that ER stress participated in regulating
Cu-induced pyroptosis in jejunal epithelial cells via the IRE1α-XBP1 pathway, which provided a novel view into the
toxicology of Cu.
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pig jejunal epitheliumelevated fluorescence signalsjejunal epithelial cellser stress participatedexcess cu treatmenter stress inhibitorj2 cellser stressire1α inhibitorxbp1 pathwayvivo vitro via similar effectssignificantly inhibitedresults suggestedpotential concernphenylbutyric acidnovel viewinduced toxicityhuman healthfood productsexcess intakeendoplasmic reticulumcommon additivealso alleviated