3-Acetyldeoxynivalenol induces apoptosis, barrier dysfunction and endoplasmic reticulum stress by inhibiting mTORC1-dependent autophagy in porcine enterocytes

3-Acetyldeoxynivalenol (3-Ac-DON), the acetylated form of deoxynivalenol, which is widely present in mycotoxin-contaminated food, feed as well as in other natural sources. Ingestion of 3-Ac-DON may result in intestinal dysfunction, leading to gut diseases in humans and Animals. Nevertheless, the molecular mechanism of 3-Ac-DON in intestinal epithelial cytotoxicity remains unclear. In this study, intestinal porcine epithelial cell line 1 (IPEC-1) cells were treated with different concentrations of 3-Ac-DON for 12 h and 24 h, respectively. The results showed that 3-Ac-DON caused cell viability decrease, cell cycle arrest in G1 phaseand depolarization of mitochondrial membrane potential. Also, Western blotting analysis showed that 3-Ac-DON significantly decreased the expression of tight junction proteins, inhibited Autophagy and activated endoplasmic reticulum (ER) stress in IPEC cells (P < 0.05). Further investigation demonstrated that 3-Ac-DON caused Apoptosis, ER stress and barrier dysfunction were reversed after pretreatment with the Autophagy activator rapamycin (100 nM), indicating that Autophagy plays a key role in the process of 3-Ac-DON-induced cell damage. In addition, we demonstrated that 3-Ac-DON inhibits the occurrence of Autophagy mediated by mTORC1 protein. In conclusion, our research indicated that the mTORC1 protein and Autophagy played a key role in the 3-Ac-DON-induced cytotoxic in IPEC cells, which will provide new therapeutic targets and ideas for 3-AC-DON-mediated intestinal injury.

3-Acetyldeoxynivalenol; Apoptosis; Autophagy; Barrier function; Endoplasmic reticulum stress; Mechanistic target of rapamycin complex 1.