The Antagonistic Effect of Glutamine on Zearalenone-Induced Apoptosis via PI3K/Akt Signaling Pathway in IPEC-J2 Cells

TianHu, Wang; Wang, Jingjing; Zhang, Tong; Gu, Aixin; Li, Jianping; Shan, Anshan

doi:10.3390/toxins13120891

Cited by 16 publications

(6 citation statements)

References 53 publications

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“…Follow-up experiments on this basis revealed a gradual decrease in cell activity with increasing ZEN concentration and staining time, in a dose–time effect relationship. These findings are comparable to previous results [ 35 ]. Moreover, as compared to the control group, ZEN significantly reduced the TEER values, suggesting an influence of ZEN on IPEC-J2 cell barrier integrity.…”

Section: Discussionsupporting

confidence: 93%

Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells

Huang

Wang

et al. 2022

IJMS

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Zearalenone (ZEN) is a widespread contaminant of cereals and agricultural products which causes food safety issues. Ingesting food or feed contaminated with ZEN can disrupt the intestinal epithelial barrier function. The RhoA/ROCK signaling pathway plays a key role in regulating the epithelial barrier function, but studies on such roles have rarely focused on the intestine. The aim of this experiment was to investigate the exact mechanism of ZEN-induced intestinal barrier damage and whether the RhoA/ROCK signaling pathway is involved. The results showed that ZEN significantly induced alkaline phosphatase (AP) activity and FITC–dextran (4 kDa) passage across the epithelial barrier, which significantly reduced the transepithelial resistance (TEER). Meanwhile, ZEN could induce the significantly down-regulated mRNA expression of tight junction proteins (occludin, claudin-1, ZO-1, and claudin-3) and redistribution of ZO-1 immunofluorescence. Further studies demonstrated that ZEN exposure activated the RhoA/ROCK signaling pathway, significantly up-regulated the mRNA expression of ROCK1, the main effector of the signaling pathway, the protein expression of phosphorylated myosin light chain (MLC) and myosin light chain kinase (MLCK), and relatively increased the activity of ATP in cells, simultaneously remodeling the cytoskeleton (F-actin). Overall, our study indicated that ZEN induced intestinal barrier dysfunction by activating the RhoA/ROCK signaling pathway.

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Section: Discussionsupporting

confidence: 93%

Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells

Huang

Wang

et al. 2022

IJMS

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“…Glutamine, a dietary amino acid, has been reported to alleviate mycotoxin-induced porcine intestinal epithelial cell injury. 48 Deoxynivalenol (DON) is the most common mycotoxin in the feed of livestock, poultry, and aquatic animals, and pigs are the most sensitive animals to DON. DON inhibits cell proliferation by inhibiting the expression of the β-catenin and c-Myc proteins.…”

Section: ■ Discussionmentioning

confidence: 99%

Glutamine Promotes Porcine Intestinal Epithelial Cell Proliferation through the Wnt/β-Catenin Pathway

Fang,

Lu,

Cheng

et al. 2024

J. Agric. Food Chem.

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Glutamine (Gln) is a critical nutrient required by neonatal mammals for intestinal growth, especially for newborn piglets. However, the mechanisms underlying the role of Gln in porcine intestinal epithelium development are not fully understood. The objective of the current study was to explore the possible signaling pathway involved in the promotion of porcine intestinal epithelial cell (IPEC-J2) proliferation by Gln. The results showed that 1 mM Gln promoted IPEC-J2 cell proliferation, and tandem mass tag proteomics revealed 973 differentially expressed proteins in Gln-treated IPEC-J2 cells, 824 of which were upregulated and 149 of which were downregulated. Moreover, gene set enrichment analysis indicated that the Wnt signaling pathway is activated by Gln treatment. Western blotting analysis further confirmed that Gln activated the Wnt/β-catenin signaling pathway. In addition, Gln increased not only cytosolic β-catenin but also nuclear β-catenin protein expression. LF3 (a β-catenin/TCF4 interaction inhibitor) assay and β-catenin knockdown demonstrated that Gln-mediated promotion of Wnt/β-catenin signaling and cell proliferation were blocked. Furthermore, the inhibition of TCF4 expression suppressed Gln-induced cell proliferation. These findings further confirmed that Wnt/β-catenin signaling is involved in the promotion of IPEC-J2 cell proliferation by Gln. Collectively, these findings demonstrated that Gln positively regulated IPEC-J2 cell proliferation through the Wnt/β-catenin pathway. These data greatly enhance the current understanding of the mechanism by which Gln regulates intestinal development.

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“…Mycotoxins enter the body and break down the physical barrier of the animal’s intestinal tract, hindering the rapid response of the body’s immune organs [ 19 , 20 ]. The intestinal epithelial cell layer is the first barrier that prevents mycotoxins from entering lower tissues [ 21 ], and multiple functions of the intestinal epithelium contribute to maintain intestinal homeostatic balance [ 22 ]. Dysfunctional intestinal barrier integrity caused by toxins and pathogens is associated with a variety of gastrointestinal disorders and diseases [ 23 ].…”

Section: Discussionmentioning

confidence: 99%

Quercetin Attenuates the Combined Effects of Zearalenone and Lipopolysaccharide on IPEC-J2 Cell Injury through Activating the Nrf2 Signaling Pathway

Wang,

Fu,

Wang

et al. 2023

Toxins

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Zearalenone (ZEA) is a mycotoxin with an estrogen-like effect that is widely found in feed. Lipopolysaccharides (LPS) derived from Gram-negative bacteria are a common endotoxin, and both toxins have effects on human and livestock health. During animal feeding, ZEA as an exotoxin and LPS as an endotoxin have the potential to co-exist in organisms. At present, other studies have only focused on the hazards of single toxins, but there are fewer studies on the coexistence and interaction between ZEA and LPS. Therefore, a further study to investigate the combined toxic effects of different concentrations of ZEA and LPS is warranted. Quercetin (QUE) is a natural flavonoid compound with strong antioxidant and anti-inflammatory properties. It is unclear whether QUE can mitigate the combined effects of ZEA and LPS. IPEC-J2, isolated from the jejunum of non-breastfed neonatal piglets, is an ideal model for the study of epithelial cell transport, intestinal bacterial interactions, and the nutrient modulation of intestinal function. Therefore, the purpose of the present study was to demonstrate the effect of QUE in alleviating the combined toxic effect of ZEA and LPS on IPEC-J2 cell damage. Cell viability was measured after treating IPEC-J2 cells sequentially with 10, 20, 30, 40, 60, 80, and 100 μM ZEA, 1, 10, 50, and 100 μg/mL LPS, and 20, 40, 60, 80, 100, and 200 μM QUE for 24 h. Based on the cell viability results, 20 μM ZEA and 1 μg/mL LPS were selected as the most suitable concentrations for further analysis. For QUE, 20 μM increased the cell viability, while 40–200 μM QUE decreased the cell viability. Therefore, for the subsequent study, 20 μM QUE was selected in combination with 20 μM ZEA and 1 μg/mL LPS. The results showed that QUE increased the cellular viability and decreased the LDH content more compared to the effects of the ZEA+LPS group. At the gene level, QUE addition up-regulated the expression of Nrf2, HO-1, SOD2, and NQO1 at the gene or protein level compared to those of the ZEA+LPS group. The measurement of tight junction-related genes and proteins showed QUE up-regulated the expression of Claudin, ZO-1, and Occludin genes and proteins more than in the ZEA+LPS group. QUE addition reduced the rate of apoptosis more than that in the ZEA+LPS group. The expressions of Bcl-2 and Bax were examined at the gene level, and QUE addition significantly reduced the Bax gene expression level compared to that of the ZEA+LPS group, but there was no apparent variation in the expression level of Bcl-2. In summary, QUE can alleviate the combined toxic effects of ZEA and LPS on IPEC-J2 cells via modulating the Nrf2 signaling pathway, up-regulating the expression of antioxidative genes, and enhancing the intestinal barrier.

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The Antagonistic Effect of Glutamine on Zearalenone-Induced Apoptosis via PI3K/Akt Signaling Pathway in IPEC-J2 Cells

Cited by 16 publications

References 53 publications

Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells

Zearalenone-Induced Mechanical Damage of Intestinal Barrier via the RhoA/ROCK Signaling Pathway in IPEC-J2 Cells

Glutamine Promotes Porcine Intestinal Epithelial Cell Proliferation through the Wnt/β-Catenin Pathway

Quercetin Attenuates the Combined Effects of Zearalenone and Lipopolysaccharide on IPEC-J2 Cell Injury through Activating the Nrf2 Signaling Pathway

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