Transcription Factor FOXO3a Is a Negative Regulator of Cytotoxicity of Fusarium mycotoxin in GES-1 Cells

文献类型： 外文期刊

第一作者： Yang, Yunxia

作者： Yang, Yunxia;Yu, Song;Liu, Na;Wu, Aibo;Xu, Haibin;Gong, Yunyun;Wu, Yongning;Gong, Yunyun;Wang, Peilong;Su, Xiaoou;Liao, Yucai;De Saeger, Sarah;Humpf, Hans-Ulrich

作者机构：

关键词： mitochondrial dysfunction; oxidative stress; FOXO3a nuclear translocation; ROS/JNK/FOXO3a; DAF16

期刊名称：TOXICOLOGICAL SCIENCES （ 影响因子：4.849； 五年影响因子：4.996 ）

ISSN： 1096-6080

年卷期： 2018 年 166 卷 2 期

页码：

收录情况： SCI

摘要： Molecular mechanism and key factors responsible for cytotoxicity against mycotoxin deoxynivalenol (DON) from Fusarium pathogens are rarely elucidated. In this study, rapid increases of ROS were first observed in human gastric epithelial (GES-1) cells under DON exposure. Mitochondrial DNA damage, impaired respiratory chain, and decreased oxygen consumption rate (OCR) values, as well as G2/M cell cycle arrest and apoptosis, were also detected. Via combinatorial approaches of a large-scale microarray of differentially expressed genes, high content and RNAi analysis, a transcription factor of Forkhead box O3 (FOXO3a) was found with crucial functionalities, regulated some apoptotic genes associated with mitochondrial toxicity and cell death after activation by nuclear translocation. Namely, knockdown of FOXO3a decreased the cytotoxicity of DON to GES-1 cells. Moreover, knockdown of the FOXO ortholog DAF16 in Caenorhabditis elegans increased the resistance to DON-induced cytotoxicity. Simultaneously, the signaling pathway of ROS/JNK/FOXO3a of DON-induced cytotoxicity was newly proposed. In total, FOXO3a via ROS/JNK/FOXO3a plays a critical role to function as negative regulator associating with DON-induced cytotoxicity, with the potential extending to other substances.

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