Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells

Yu, Song; Jia, Bingxuan; Yang, Yunxia; Liu, Na; Wu, Aibo

doi:10.1016/j.fct.2019.111080

Cited by 30 publications

(29 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that the endoplasmic reticulum (ER) stress is activated and induces cell death when the cells are threatened by the external environment [ 34 ]. Our previous study has shown that FB1 can induce ER stress in GES-1 cells [ 10 ]. We verified whether FB2 and FB3 caused ER stress in GES-1 cells.…”

Section: Resultsmentioning

confidence: 99%

“…Our previous studies have shown that the disruption of sphingolipid metabolism by the inhibition of the ceramide synthase leading to the accumulation of intracellular free sphingoid bases plays an important role in FB1-induced GES-1 cytotoxicity [ 10 ]. We then examined whether the disruption of a sphingolipid metabolism also plays an important role in the GES-1 cytotoxicity induced by FB2 and FB3.…”

Section: Resultsmentioning

confidence: 99%

“…In 2001, a survey of mycotoxin contamination on 4327 grain samples worldwide showed that for major fumonisin B (FBs) positive rates were approximately 27%, 51%, 58%, 56%, and 55%, respectively, in North America, Central Europe, Africa, South Asia, and Southeast Asia. The prevalence in South America was the highest, with a positive rate of 76% (average level of 1.50 mg/kg) [ 10 ]. The content of FB contaminators in compound feed and feed ingredients was 93.33% and 83.33%.…”

Section: Introductionmentioning

confidence: 99%

“…In order to obey the rules of 3R, the human gastric epithelial cell line (GES-1) was used in this study as an in vitro model to evaluate the toxicity of FBs, a class of common fumonisins. Our previous research indicated that the cytotoxicity induced by FB1 was not obvious at 24 h, while all groups (2.5–40 µM) could significantly induce cytotoxicity at 48 h [ 10 ]. Therefore, this experiment chose the timepoint of 48 h as the exposure time.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Evaluation of the Individual and Combined Toxicity of Fumonisin Mycotoxins in Human Gastric Epithelial Cells

Jia

Liu

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

Fumonisin contaminates food and feed extensively throughout the world, causing chronic and acute toxicity in human and animals. Currently, studies on the toxicology of fumonisins mainly focus on fumonisin B1 (FB1). Considering that FB1, fumonisin B2 (FB2) and fumonisin B3 (FB3) could coexist in food and feed, a study regarding a single toxin, FB1, may not completely reflect the toxicity of fumonisin. The gastrointestinal tract is usually exposed to these dietary toxins. In our study, the human gastric epithelial cell line (GES-1) was used as in vitro model to evaluate the toxicity of fumonisin. Firstly, we found that they could cause a decrease in cell viability, and increase in membrane leakage, cell death and the induction of expression of markers for endoplasmic reticulum (ER) stress. Their toxicity potency rank is FB1 > FB2 >> FB3. The results also showed that the synergistic effect appeared in the combinations of FB1 + FB2 and FB1 + FB3. Nevertheless, the combinations of FB2 + FB3 and FB1 + FB2 + FB3 showed a synergistic effect at low concentration and an antagonistic effect at high concentration. We also found that myriocin (ISP-1) could alleviate the cytotoxicity induced by fumonisin in GES-1 cells. Finally, this study may help to determine or optimize the legal limits and risk assessment method of mycotoxins in food and feed and provide a potential method to block the fumonisin toxicity.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Evaluation of the Individual and Combined Toxicity of Fumonisin Mycotoxins in Human Gastric Epithelial Cells

Jia

Liu

et al. 2020

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

“…Furthermore, it could be shown that the stimulation of SNO cells with 1.25 µM FB1 led to the induction of apoptosis [38]. Stimulation with FB1 also led to increased apoptosis in Ges-1 cells [39]. Moreover, SKI II was also shown to induce apoptosis in HL-60 and U937 cells [40], in RNK-16 and NKL cells [41], and in HeLa and SiHa cells as well [42].…”

Section: Discussionmentioning

confidence: 95%

Sorafenib Treatment and Modulation of the Sphingolipid Pathway Affect Proliferation and Viability of Hepatocellular Carcinoma In Vitro

Jakobi

Beyer

Koch

et al. 2020

IJMS

View full text Add to dashboard Cite

Hepatocellular carcinoma (HCC) shows a remarkable heterogeneity and is recognized as a chemoresistant tumor with dismal prognosis. In previous studies, we observed significant alterations in the serum sphingolipids of patients with HCC. This study aimed to investigate the in vitro effects of sorafenib, which is the most widely used systemic HCC medication, on the sphingolipid pathway as well as the effects of inhibiting the sphingolipid pathway in HCC. Huh7.5 and HepG2 cells were stimulated with sorafenib, and inhibitors of the sphingolipid pathway and cell proliferation, viability, and concentrations of bioactive metabolites were assessed. We observed a significant downregulation of cell proliferation and viability and a simultaneous upregulation of dihydroceramides upon sorafenib stimulation. Interestingly, fumonisin B1 (FB1) and the general sphingosine kinase inhibitor SKI II were able to inhibit cell proliferation more prominently in HepG2 and Huh7.5 cells, whereas there were no consistent effects on the formation of dihydroceramides, thus implying an involvement of distinct metabolic pathways. In conclusion, our study demonstrates a significant downregulation of HCC proliferation upon sorafenib, FB1, and SKI II treatment, whereas it seems they exert antiproliferative effects independently from sphingolipids. Certainly, further data would be required to elucidate the potential of FB1 and SKI II as putative novel therapeutic targets in HCC.

show abstract

Resveratrol alleviates fumonisin‐induced intestinal cytotoxicity by modulating apoptosis, tight junction, and inflammation in IPEC‐J2 porcine intestinal epithelial cells

Yu,

Zou,

Zhao

et al. 2023

Environmental Toxicology

Self Cite

View full text Add to dashboard Cite

Fumonisins are common contaminants in the global food and environment, pose a variety of health risks to humans and animals. However, the method of mitigating fumonisin toxicity is still unclear. Resveratrol is a natural compound with antioxidant and anti‐inflammatory properties. In this study, the protective effect of resveratrol against fumonisin‐induced intestinal toxicity was investigated by the porcine intestinal epithelial cell line (IPEC‐J2). The cells were treated with 0–40 μM fumonisin for 24 or 48 h with or without the 24 h resveratrol (15 μM) pretreatment. The data showed that resveratrol could alleviate the fumonisin B1 (FB1)‐induced decrease in cell viability and amplify in membrane permeability. At the same time, it could reduce the accumulation of intracellular reactive oxygen species and increase the expression ranges of Nrf2 and downstream genes (SOD1 and NQO‐1), thereby counteracting FB1‐induced apoptosis. Furthermore, resveratrol was able to reduce the expression levels of inflammatory factors (TNF‐α, IL‐1β, and IL‐6), increase the expression levels of tight junction proteins (Claudin‐1, Occludin, and ZO‐1), and the integrity of the IPEC‐J2 monolayer. Our data also showed that resveratrol could attenuate the toxicity of the co‐occurrence of three fumonisins. It is implied that resveratrol represents a promising protective approach for fumonisin, even other mycotoxins in the future. This provided a new strategy for further blocking and controlling the toxicity of fumonisin, subsequently avoiding adverse effects on the human and animal health.

show abstract

Involvement of PERK-CHOP pathway in fumonisin B1- induced cytotoxicity in human gastric epithelial cells

Cited by 30 publications

References 46 publications

Evaluation of the Individual and Combined Toxicity of Fumonisin Mycotoxins in Human Gastric Epithelial Cells

Evaluation of the Individual and Combined Toxicity of Fumonisin Mycotoxins in Human Gastric Epithelial Cells

Sorafenib Treatment and Modulation of the Sphingolipid Pathway Affect Proliferation and Viability of Hepatocellular Carcinoma In Vitro

Resveratrol alleviates fumonisin‐induced intestinal cytotoxicity by modulating apoptosis, tight junction, and inflammation in IPEC‐J2 porcine intestinal epithelial cells

Contact Info

Product

Resources

About