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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