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Deoxynivalenol-Induced Cytotoxicity and Apoptosis in IPEC-J2 Cells Through the Activation of Autophagy by Inhibiting PI3K-AKT-mTOR Signaling Pathway

Published:24 October 2019 DOI: 10.1021/acsomega.9b03208 PMID: 31720552
Xiaolian Gu, Wenyan Guo, Yujie Zhao, Gang Liu, Jine Wu*, Chao Chang*

Abstract

With the purpose to explore the relationship between deoxynivalenol (DON)-induced apoptosis and autophagy and provide mechanistic explanations for the toxic effects of DON on IPEC-J2 cells, we determined the cell viability, cell morphology, apoptosis, and autophagy by using autophagy inhibitor 3-methyladenine (3-MA), PI3K pathway inhibitor LY294002, and activator 740Y-P. It turned out that 3-MA was able to attenuate the reduction of cell viability induced by DON. Moreover, 3-MA was capable of upregulating the expression of DON-induced autophagic protein p62 and downregulating the expressions of DON-induced autophagic protein LC3-II and apoptotic protein Bax, suggesting that autophagy is a driving mechanism for this apoptotic induction. The results of Annexin V-FITC/PI double staining indicated that DON could induce apoptosis by inhibiting the PI3K-AKT-mTOR signaling pathway. Subsequently, it was further confirmed by Western blot analysis that DON significantly decreased expressions of P-AKT/AKT, p-mTOR/mTOR, and autophagic protein p62, and increased expression of autophagy-related protein LC3-II, suggesting that DON triggered autophagy by inhibiting the PI3K-AKT-mTOR signaling pathway. To conclude, these data reveal that DON may induce cytotoxicity and apoptosis through the activation of autophagy by suppressing the PI3K-AKT-mTOR signaling pathway. This study provides new insights into the mechanisms by which DON incurs cytotoxic effects.

Substances (4)

Materials
Procduct Name CAS Molecular Formula Supplier Price
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 406 suppliers $12.00-$3350.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 406 suppliers $12.00-$3350.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 406 suppliers $12.00-$3350.00
LY 294002 Hydrochloride 154447-36-6 C19H17NO3 406 suppliers $12.00-$3350.00

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