Department of Pathology, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China.
Environ Toxicol. 2024 Jan;39(1):277-288. doi: 10.1002/tox.23943. Epub 2023 Sep 13.
Deoxynivalenol (DON) is a mycotoxin frequently occurring in human and animal food worldwide, which raises increasing public health concerns. In the present study, we used human keratinocytes (HaCaT cells) as an in vitro model to explore the cytotoxic effect of DON. The results showed that the cells exhibited varying degrees of damage, including decreased cell number and viability, cell shrinkage and floating, when treated with 0.125, 0.25, and 0.5 μg/mL DON for 6, 12, and 24 h, respectively. Furthermore, exposure to DON for 24 h significantly increased the lactate dehydrogenase (LDH) release and intracellular reactive oxygen species (ROS), and prominently decreased the superoxide dismutase (SOD) and catalase (CAT) activity. Additionally, DON exposure induced mitochondrial damage and cell apoptosis through reducing mitochondrial membrane potential. Then, we performed RNA-sequencing to investigate the molecular changes in HaCaT cells after DON exposure. The RNA-sequencing results revealed that DON exposure altered the gene expression involved in apoptosis, MAPK signaling pathway, and PI3K/Akt signaling pathway. Moreover, DON exposure significantly decreased the mRNA and protein expression of Bcl-2, and increased the mRNA and protein expression of Bax, Caspase 3 and COX-2, the protein expression of PI3K, and the phosphorylation levels of Akt, ERK, p38, and JNK. Taken together, these findings suggest that DON exposure could induce cell damage, oxidative stress, and apoptosis in HaCaT cells through the activation of PI3K/Akt and MAPK pathways.
脱氧雪腐镰刀菌烯醇（DON）是一种在全球范围内普遍存在于人类和动物食品中的真菌毒素，这引起了公众对健康问题的日益关注。在本研究中，我们使用人角质形成细胞（HaCaT 细胞）作为体外模型来研究 DON 的细胞毒性作用。结果表明，当用 0.125、0.25 和 0.5μg/mL DON 处理细胞 6、12 和 24h 时，细胞表现出不同程度的损伤，包括细胞数量和活力下降、细胞皱缩和漂浮。此外，暴露于 DON 24h 后显著增加乳酸脱氢酶（LDH）释放和细胞内活性氧（ROS）水平，并显著降低超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性。此外，DON 暴露通过降低线粒体膜电位诱导线粒体损伤和细胞凋亡。然后，我们进行了 RNA 测序，以研究 DON 暴露后 HaCaT 细胞的分子变化。RNA 测序结果表明，DON 暴露改变了与细胞凋亡、MAPK 信号通路和 PI3K/Akt 信号通路相关的基因表达。此外，DON 暴露显著降低了 Bcl-2 的 mRNA 和蛋白表达，增加了 Bax、Caspase 3 和 COX-2 的 mRNA 和蛋白表达、PI3K 的蛋白表达以及 Akt、ERK、p38 和 JNK 的磷酸化水平。总之，这些发现表明 DON 暴露可通过激活 PI3K/Akt 和 MAPK 通路诱导 HaCaT 细胞损伤、氧化应激和细胞凋亡。
