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

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

  • Chem Biol Interact. 2023 Aug 31;110695. doi: 10.1016/j.cbi.2023.110695.
Tongkun Zhang 1,  Jun Bai 1,  Guangye Chen 2,  Zhaohui Chen 1,  Shenming Zeng 1,  Ying Yang 1,  Zhenlong Wu 3
Affiliations

Affiliations

  • 1 State Key Laboratory of Animal Nutrition and Feeding, Department of Companion Animal Science, China Agricultural University, Beijing, 100193, China.
  • 2 SILC Besiness School, Shanghai University, Shanghai, 200444, China.
  • 3 State Key Laboratory of Animal Nutrition and Feeding, Department of Companion Animal Science, China Agricultural University, Beijing, 100193, China. Electronic address: [email protected].
PMID: 37659622 DOI: 10.1016/j.cbi.2023.110695
Abstract

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.

Keywords

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

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