Phosphoproteome Analysis Reveals the Molecular Mechanisms Underlying Deoxynivalenol-Induced Intestinal Toxicity in IPEC-J2 Cells.
Deoxynivalenol (DON) is a widespread trichothecene mycotoxin that commonly contaminates cereal crops and has various toxic effects in animals and humans. DON primarily targets the gastrointestinal tract, the first barrier against ingested food contaminants. In this study, an isobaric tag for relative and absolute quantitation (iTRAQ)-based phosphoproteomic approach was employed to elucidate the molecular mechanisms underlying DON-mediated intestinal toxicity in porcine epithelial cells (IPEC-J2) exposed to 20 μM DON for 60 min. There were 4153 unique phosphopeptides, representing 389 phosphorylation sites, detected in 1821 phosphoproteins. We found that 289 phosphopeptides corresponding to 255 phosphoproteins were differentially phosphorylated in response to DON. Comprehensive Gene Ontology (GO) analysis combined with Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment revealed that, in addition to previously well-characterized mitogen-activated protein kinase (MAPK) signaling, DON exposure altered phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and Janus kinase/signal transducer, and activator of transcription (JAK/STAT) pathways. These pathways are involved in a wide range of biological processes, including apoptosis, the intestinal barrier, intestinal inflammation, and the intestinal absorption of glucose. DON-induced changes are likely to contribute to the intestinal dysfunction. Overall, identification of relevant signaling pathways yielded new insights into the molecular mechanisms underlying DON-induced intestinal toxicity, and might help in the development of improved mechanism-based risk assessments in animals and humans.
Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture, Beijing 100081, China. zzq19830619@163.com.
Zhi-Qi
ZQ
Zhang
College of Animal Science and National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510642, China. songbowang@scau.edu.cn.
Song-Bo
SB
Wang
Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture, Beijing 100081, China. wangruiguo@caas.cn.
Rui-Guo
RG
Wang
Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture, Beijing 100081, China. zhangwei03@caas.cn.
Wei
W
Zhang
Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture, Beijing 100081, China. wangpeilong@caas.cn.
Pei-Long
PL
Wang
Institute of Quality Standards and Testing Technology for Agricultural Products, Chinese Academy of Agricultural Science, Key Laboratory of Agrifood Safety and Quality, Ministry of Agriculture, Beijing 100081, China. suxiaoou@caas.cn.
Xiao-Ou
XO
Su
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D010750:Phosphoproteins / Q000378:metabolism*; D020543:Proteome; D013552:Swine; D062725:Tight Junction Proteins / Q000378:metabolism; D014255:Trichothecenes / Q000633:toxicity*
D010750:Phosphoproteins; D020543:Proteome; D062725:Tight Junction Proteins; D014255:Trichothecenes; D005947:Glucose; C007262:deoxynivalenol
deoxynivalenol; intestinal toxicity; phosphoproteomics; signaling pathways
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