Beijing Jihua Biotechnology Services Co., LTD, Beijing 102200, China.
College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China.
Toxins (Basel). 2020 Oct 29;12(11):681. doi: 10.3390/toxins12110681.
Patulin (PAT) is a natural mycotoxin that commonly contaminates fruits and fruit-based products. Previous work indicated that PAT-induced apoptosis in which reactive oxygen species (ROS) are involved in human embryonic kidney (HEK293) cells. To uncover novel aspects of the possible mechanism of PAT nephrotoxicity, the transcriptome and proteome profiles were investigated using the digital gene expression (DGE) and isobaric tags for relative and absolute quantitation (iTRAQ) proteomic approaches. A total of 127 genes and 85 proteins were found to express differentially in response to 5 μM PAT for 10 h in HEK293 cells. The most dramatic changes of expression were noticed with genes or proteins related to apoptosis, oxidative phosphorylation ribosome and cell cycle. Especially, the activation of caspase 3, UQCR11, active transport form and endocytosis appeared to be crucial in PAT kidney cytotoxicity. PAT also seemed to be associated with cancer and neuropathic disease as pathways associated with carcinogenesis, Alzheimer's disease and Parkinson's disease were induced. Overall, this study served to uncover overall insights associated with signaling pathway that modulated the PAT toxicity mechanism.
棒曲霉素（PAT）是一种天然真菌毒素，普遍存在于水果及其制品中。先前的研究表明，棒曲霉素可诱导人胚肾（HEK293）细胞发生细胞凋亡，而活性氧（ROS）在此过程中发挥作用。为了揭示棒曲霉素肾毒性的可能机制的新方面，我们采用数字基因表达（DGE）和同位素标记相对和绝对定量（iTRAQ）蛋白质组学方法研究了转录组和蛋白质组图谱。在 HEK293 细胞中，用 5 μM PAT 处理 10 h 后，发现有 127 个基因和 85 种蛋白质的表达出现差异。与细胞凋亡、氧化磷酸化核糖体和细胞周期相关的基因或蛋白质的表达变化最为显著。特别是，半胱氨酸天冬氨酸蛋白酶 3、UQCR11、主动运输形式和内吞作用的激活似乎在 PAT 肾细胞毒性中起着关键作用。PAT 似乎还与癌症和神经病变疾病有关，因为与癌症发生、阿尔茨海默病和帕金森病相关的途径被激活。总的来说，本研究揭示了与信号通路相关的总体见解，这些信号通路调节了 PAT 的毒性机制。
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