The Key Laboratory for Space Bioscience and Biotechnology, School of Life Sciences, Northwestern Polytechnical University, Xi'an, Shaanxi 710072, China.
No. 889, Xi'an Institute for Food and Drug, Cangtai West Road, Chang'an District, Xi'an, Shaanxi, 710700, China.
Toxicology. 2023 Aug 1;494:153593. doi: 10.1016/j.tox.2023.153593. Epub 2023 Jul 12.
The intestinal epithelial barrier plays a crucial role in maintaining human and animal health. Deoxynivalenol (DON) is a mycotoxin that contaminates cereal-based foods worldwide, which is a serious threat to human and animal health. This study was aimed to investigate the protective effect of selenium nanoparticles (SeNPs) synthesized by Lactobacillus casei ATCC 393 against DON-induced intestinal epithelial barrier dysfunction and its relationship with PERK-mediated signaling pathway. IPEC-J2 cells were randomly assigned to four groups: Con (vehicle), DON (0.6 μg DON/mL, 48 h), SeNPs+DON (8 μg Se/mL, 24 h; 0.6 μg DON/mL, 48 h) and SeNPs (8 μg Se/mL, 24 h). Compared with Con group, the transepithelial electrical resistance (TEER) and the tight junction proteins expression of IPEC-J2 cells exposed to DON was increased and decreased, respectively. In addition, DON exposure led to increased ROS content, decreased antioxidant capacity, structural damage of endoplasmic reticulum (ER), and activation of endoplasmic reticulum stress (ERS)-related protein kinase R-like endoplasmic reticulum kinase (PERK) pathway in IPEC-J2. Compared with SeNPs+DON group, SeNPs alleviated oxidative stress, ER structure damage and PERK pathway activation and the increase of intestinal epithelial permeability of IPEC-J2 cells exposed to DON. PERK agonist (CCT020312) and inhibitor (GSK2656157) treatments were performed to identify the role of PERK signaling pathway in the regulatory effects of SeNPs on DON-induced intestinal epithelial barrier dysfunction. Compared with SeNPs+DON group, PERK agonist increased the expression levels of p-PERK. PERK inhibitor exerted a similar inhibitory effect to SeNPs on the p-PERK expression. In conclusion, SeNPs effectively alleviate DON-induced intestinal epithelial barrier dysfunction in IPEC-J2 cells, which are closely associated with ERS-related PERK signaling pathway. This will provide a potential solution for prevention and control of DON in the aquaculture industry.
肠上皮屏障在维持人类和动物健康方面起着至关重要的作用。脱氧雪腐镰刀菌烯醇（DON）是一种污染全世界谷物类食物的真菌毒素，对人类和动物健康构成严重威胁。本研究旨在探讨由干酪乳杆菌 ATCC 393 合成的硒纳米粒子（SeNPs）对 DON 诱导的肠上皮屏障功能障碍的保护作用及其与 PERK 介导的信号通路的关系。IPEC-J2 细胞被随机分为四组：Con（对照）、DON（0.6μg DON/mL，48 小时）、SeNPs+DON（8μg Se/mL，24 小时；0.6μg DON/mL，48 小时）和 SeNPs（8μg Se/mL，24 小时）。与 Con 组相比，暴露于 DON 的 IPEC-J2 细胞的跨上皮电阻（TEER）和紧密连接蛋白表达增加和减少，分别。此外，DON 暴露导致 ROS 含量增加，抗氧化能力降低，内质网（ER）结构损伤，以及 IPEC-J2 中内质网应激（ERS）相关蛋白激酶 R 样内质网激酶（PERK）通路的激活。与 SeNPs+DON 组相比，SeNPs 减轻了 DON 暴露的 IPEC-J2 细胞的氧化应激、ER 结构损伤和 PERK 通路激活以及肠上皮通透性的增加。进行 PERK 激动剂（CCT020312）和抑制剂（GSK2656157）处理，以确定 PERK 信号通路在 SeNPs 对 DON 诱导的肠上皮屏障功能障碍的调节作用中的作用。与 SeNPs+DON 组相比，PERK 激动剂增加了 p-PERK 的表达水平。PERK 抑制剂对 p-PERK 的表达也表现出与 SeNPs 相似的抑制作用。综上所述，SeNPs 有效缓解了 DON 诱导的 IPEC-J2 细胞肠上皮屏障功能障碍，这与 ERS 相关的 PERK 信号通路密切相关。这将为水产养殖业中 DON 的预防和控制提供一种潜在的解决方案。
