Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou 225009, China.
National Engineering Laboratory for Animal Breeding and MOA Key Laboratory of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100093, China.
J Agric Food Chem. 2022 Jun 1;70(21):6561-6572. doi: 10.1021/acs.jafc.2c01107. Epub 2022 May 18.
Zearalenone (ZEA) is a mycotoxin that frequently occurs in agricultural crops and related products and seriously threatens both animal feed and human food safety. To identify key metabolites and regulators involved in ZEA toxicological processes, we performed metabolomic and transcriptomic analyses of porcine IPEC-J2 intestinal epithelial cells upon ZEA exposure using liquid chromatography-mass spectrometry (LC-MS)/MS and RNA-seq techniques. A total of 325 differential metabolites and 5646 differentially expressed genes were detected. Integrated analyses of metabolomic and transcriptomic data indicated that metabolic processes including lipid metabolism, amino acid metabolism, and carbohydrate metabolism were most affected. Exogenous addition of the key metabolite l-arginine significantly facilitated ZEA metabolism and ameliorated ZEA-induced reactive oxygen species levels and cell apoptosis. Furthermore, l -arginine contributed to the expression of phase II detoxification genes (SULT2B1, GSTA1, GSTM3, and GPX4). l-Arginine addition also increased the protein levels of LC3-II and Beclin 1, and downregulated p62/SQSTM1 levels, indicating its regulatory roles in autophagic flux activation upon ZEA exposure. This study provided global insights into metabolic and transcriptional changes as well as key metabolites and regulators underlying the cellular response to ZEA exposure, and paved the way for the identification of metabolic and molecular targets for biomonitoring and controlling contamination by ZEA.
玉米赤霉烯酮（ZEA）是一种经常出现在农作物及相关产品中的真菌毒素，严重威胁着动物饲料和人类食品安全。为了鉴定参与 ZEA 毒理学过程的关键代谢物和调控因子，我们使用液相色谱-质谱联用（LC-MS/MS）和 RNA 测序技术，对 ZEA 暴露后猪肠上皮细胞（IPEC-J2）进行了代谢组学和转录组学分析。共检测到 325 个差异代谢物和 5646 个差异表达基因。代谢组学和转录组学数据的综合分析表明，代谢过程包括脂质代谢、氨基酸代谢和碳水化合物代谢受到的影响最大。关键代谢物 l-精氨酸的外源添加显著促进了 ZEA 的代谢，并改善了 ZEA 诱导的活性氧水平和细胞凋亡。此外，l-精氨酸有助于 II 相解毒基因（SULT2B1、GSTA1、GSTM3 和 GPX4）的表达。l-精氨酸的添加还增加了 LC3-II 和 Beclin 1 的蛋白水平，并下调了 p62/SQSTM1 水平，表明其在 ZEA 暴露时对自噬流激活的调控作用。本研究提供了对细胞对 ZEA 暴露反应的代谢和转录变化以及关键代谢物和调控因子的全面认识，为鉴定代谢和分子靶标以进行 ZEA 污染的生物监测和控制铺平了道路。
