1. Academic Validation
  2. Endoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis via Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells

Endoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis via Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells

  • J Agric Food Chem. 2022 Feb 2;70(4):1293-1303. doi: 10.1021/acs.jafc.1c07927.
Jianzhao Liao 1 Zhuoying Hu 1 Quanwei Li 1 Hongji Li 1 Weijin Chen 1 Haihua Huo 1 Qingyue Han 1 Hui Zhang 1 Jianying Guo 1 Lianmei Hu 1 Jiaqiang Pan 1 Ying Li 1 Zhaoxin Tang 1
Affiliations

Affiliation

  • 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, Guangdong, P. R. China.
Abstract

Copper (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.

Keywords

IRE1α-XBP1 pathway; copper; endoplasmic reticulum stress; jejunal epithelial cell; pyroptosis.

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