Transcription Factor FOXO3a Is a Negative Regulator of Cytotoxicity of Fusarium mycotoxin in GES-1 Cells
Abstract
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 poten...Continue Reading
References
FoxO3a Mediates the Inhibitory Effects of the Antiepileptic Drug Lamotrigine on Breast Cancer Growth
Autophagy Inhibition Mediates Apoptosis Sensitization in Cancer Therapy by Relieving FOXO3a Turnover
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis