College of Veterinary Medicine, South China Agricultural University, Guangzhou, China.
J Appl Toxicol. 2022 Apr;42(4):660-670. doi: 10.1002/jat.4248. Epub 2021 Oct 30.
Zearalenone (ZEA) is one of the most major food contaminants in cereal crops worldwide, risking health of both livestock and humans. This study aimed to assess the cytotoxicity and the underlying mechanism of ZEA on thymic epithelial cells. By using proteomics analysis, we identified 596 differentially expressed proteins in MTEC1 cells upon zearalenone exposure, of which 245 were upregulated and 351 were downregulated. Gene ontology (GO) analysis suggested that differentially expressed proteins were participated in protein synthesis, oxidative phosphorylation, and ATP binding. KEGG pathway enrichment analysis showed that differentially expressed proteins were mainly related to mitochndrial metabolism, such as citrate cycle (TCA cycle) and oxidative phosphorylation. We demonstrated that ZEA treatment was able to increase the intracellular reactive oxygen species (ROS) level, to decrease ΔΨm, ATP level, and the copy number of mtDNA, leading to necrotic cell death. Moreover, we showed that ZEA treatment inhibited cell proliferation and induced G2/M phase arrest by downregulation of proliferation-associated proteins ERK, p-ERK, CDK1, and p-CHK1. Taken together, we found that the toxicity of ZEA on thymic epithelial cells is mainly caused by the inhibition of mitochondrial dysfunction and cell proliferation. Our study might open new avenues for treatment strategies.
玉米赤霉烯酮（ZEA）是世界范围内谷物作物中主要的食品污染物之一，对牲畜和人类的健康都构成威胁。本研究旨在评估玉米赤霉烯酮对胸腺上皮细胞的细胞毒性及其潜在机制。通过蛋白质组学分析，我们在 MTEC1 细胞暴露于玉米赤霉烯酮后鉴定出 596 个差异表达蛋白，其中 245 个上调，351 个下调。GO 分析表明，差异表达蛋白参与了蛋白质合成、氧化磷酸化和 ATP 结合。KEGG 通路富集分析表明，差异表达蛋白主要与线粒体代谢有关，如柠檬酸循环（TCA 循环）和氧化磷酸化。我们证明 ZEA 处理能够增加细胞内活性氧（ROS）水平，降低ΔΨm、ATP 水平和 mtDNA 拷贝数，导致坏死性细胞死亡。此外，我们还表明，ZEA 处理通过下调增殖相关蛋白 ERK、p-ERK、CDK1 和 p-CHK1 抑制细胞增殖并诱导 G2/M 期阻滞。总之，我们发现 ZEA 对胸腺上皮细胞的毒性主要是由于线粒体功能障碍和细胞增殖的抑制所致。我们的研究可能为治疗策略开辟新的途径。
