Close association between the synergistic toxicity of zearalenone-deoxynivalenol combination and microRNA221-mediated PTEN/PI3K/AKT signaling in HepG2 cells

文献类型： 外文期刊

第一作者： Rong, Xue

作者： Rong, Xue;Jiang, Yang;Li, Feng;Li, Dapeng;Sun-Waterhouse, Dongxiao;Zhao, Shancang;Guan, Xuedong

作者机构：

关键词： Zearalenone; Deoxynivalenol; Synergistic toxicity; miR-221; PTEN/PI3K/AKT signaling pathway; HepG2 cells

期刊名称：TOXICOLOGY （ 影响因子：4.221； 五年影响因子：4.704 ）

ISSN： 0300-483X

年卷期： 2022 年 468 卷

页码：

收录情况： SCI

摘要： Mycotoxins can impart different types of combined toxicity to humans and animals, therefore, it is critical to understand the underlying mechanisms to eliminate the harm. Herein a combination of zearalenone (ZEA) at 2 mu M and deoxynivalenol (DON) at 0.1 mu M decreased cell viability and increased ROS level in HepG2 cells, suggesting synergistic toxicity exerted by ZEA and DON even at their low toxic concentrations. Moreover, apoptosis and inflammatory response were promoted after the co-exposure of ZEA and DON, indicated by the increased expression of BAX, Caspase-3, IL-1 beta and IL-6 genes. Such synergistic toxicity was closely associated with miR-221-mediated PTEN/PI3K/AKT signal pathway, with a negative regulatory relationship between PTEN and PI3K/AKT signaling. MiR-221 could influence cell viability and ROS level to counter the combined toxicity of ZEA and DON through targeting directly PTEN gene. This study demonstrated the toxicological impact of mycotoxin interactions on cells, and critical role of the interplay between miRNAs and PTEN in monitoring the synergistic toxicity of mycotoxin mixture.

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