Fumonisin B1 exposure induces apoptosis of human kidney tubular epithelial cells through regulating PTEN/PI3K/AKT signaling pathway via disrupting lipid raft formation

Song, Yanyan; Liu, Wei; Zhao, Yao; Zang, Junting; Gao, Hang

doi:10.1016/j.toxicon.2021.10.013

Cited by 14 publications

(7 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sphingomyelins tended to decrease in the liver of pigs administered FB1 orally at a dose equivalent to 25–30 mg/kg of feed, and moderate signs of toxicity were observed at this dose [ 28 ]. A reduction in sphingomyelin concentrations at cytotoxic doses of FB1 was also observed after the direct administration of FB1 to Brown Tsaiya duck embryos [ 63 ], and in cell cultures at concentrations of 20 to 250 µM of FB1 [ 20 , 21 , 22 ]. Moreover, the role of sphingomyelin in FB1-induced toxicity has been observed in mice using myriocin, which is a specific inhibitor of serine palmitoyltransferase ( Figure 1 ).…”

Section: Discussionmentioning

confidence: 98%

“…Because sphingolipid metabolism in cells is complex, the inhibition of de novo synthesis alone is not sufficient to understand all the effects fumonisins have on sphingolipids. Activation of the sphingomyelin hydrolysis and recycling pathway (Figure 1) also explains the increase in the concentrations of ceramides and sphingosine reported in some studies [4] and could play a key role in fumonisin toxicity [18][19][20][21][22]. Therefore, the fine characterization of sphingolipid alteration is necessary to understand the multiple facets of fumonisin toxicity, including differences in sensitivity among species.…”

Section: Introductionmentioning

confidence: 97%

See 1 more Smart Citation

Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity

Guerre

Travel

Tardieu

2022

IJMS

View full text Add to dashboard Cite

The effects of fumonisins on sphingolipids in turkeys are unknown, except for the increased sphinganine to sphingosine ratio (Sa:So) used as a biomarker. Fumonisins fed at 20.2 mg/kg for 14 days were responsible for a 4.4 fold increase in the Sa:So ratio and a decrease of 33% and 36% in C14-C16 ceramides and C14-C16 sphingomyelins, respectively, whereas C18-C26 ceramides and C18-C26 sphingomyelins remained unaffected or were increased. Glucosyl- and lactosyl-ceramides paralleled the concentrations of ceramides. Fumonisins also increased dihydroceramides but had no effect on deoxysphinganine. A partial least squfares discriminant analysis revealed that all changes in sphingolipids were important in explaining the effect of fumonisins. Because deoxynivalenol and zearalenone are often found in feed, their effects on sphingolipids alone and in combination with fumonisins were investigated. Feeding 5.12 mg deoxynivalenol/kg reduced dihydroceramides in the liver. Zearalenone fed at 0.47 mg/kg had no effect on sphingolipids. When fusariotoxins were fed simultaneously, the effects on sphingolipids were similar to those observed in turkeys fed fumonisins alone. The concentration of fumonisin B1 in the liver of turkeys fed fumonisins was 0.06 µmol/kg. Changes in sphingolipid concentrations differed but were consistent with the IC50 of fumonisin B1 measured in mammals; these changes could explain the relative resistance of turkeys to fumonisins.

show abstract

Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity

Guerre

Travel

Tardieu

2022

IJMS

View full text Add to dashboard Cite

show abstract

“…Accumulating evidence has shown that lipids, especially those that constitute the rafts of cellular membrane, play protective roles against the exposure of mycotoxins such as OTA and fumonisin B1, possibly via maintaining membrane properties and H + -ATPase activity [ 31 , 32 ]. This would lead to the repair of the mycotoxin-induced structural failure of the cell membrane by activating ceramide synthesis at the endoplasmic reticulum [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Lithocholic Acid Alleviates Deoxynivalenol-Induced Lethal Cholesterol Metabolic Abnormalities in IPI-2I Cells

et al. 2022

Metabolites

View full text Add to dashboard Cite

Deoxynivalenol (DON) is a secondary metabolite of fungi. Ingestion of feed containing DON causes severe intestinal damage in humans and animals, possibly due to cholesterol-enriched lipid raft abnormalities. Cholic acid (CA) and lithocholic acid (LCA) are metabolites of cholesterol transformation, which have been proven to benefit epithelial cell proliferation and reduce intestinal inflammation and lesions. Therefore, we aimed to study the protective roles of CA and LCA administration on the DON-exposed intestinal epithelial cells (IPI-2I) and the underlying mechanisms involved in cholesterol metabolism. We found that LCA pretreatment, but not CA, alleviated the reduction of cell numbers caused by DON exposure. Furthermore, we demonstrate that LCA restored the DON-induced cell apoptosis by reducing the cleaved caspase 3 and cleaved PARP-1 expression. DON-increased cellular cholesterol and bile acid contents were significantly reduced when LCA was co-treated. Further transcriptomic analysis revealed that the aberrant cholesterol homeostasis genes profile was observed in the cells exposed to DON or pretreated with LCA. We also validated that the key genes involved in cholesterol biosynthesis and transformation (cholesterol to bile acids) were strongly inhibited by the LCA treatment in the DON-exposed cells. Together, this study demonstrated that LCA ameliorated DON-caused toxic apoptosis in IPI-2I cells by maintaining cholesterol metabolism. We suggest that as an endogenous metabolite, LCA may be used as a therapeutic and/or integrated into a dietary intervention against mycotoxin toxicity.

show abstract

“…In our study, FB 1 significantly promoted the cleavage and expression of Caspase3 and Caspase9. Similarly, FB 1 induced apoptosis of HK-2 cells in a dose-dependent manner [ 32 ]. FB 1 at 50 μM (36 μg/mL) induced a large amount of DNA damage and chromatin depolymerization in SH-SY5y neuroblastoma cells, and also promoted nuclear translocation of apoptosis-inducing factors [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of Fumonisin B1 on Proliferation and Apoptosis of Intestinal Porcine Epithelial Cells

Wang

Lei

Zhou

et al. 2022

Toxins

View full text Add to dashboard Cite

Fumonisin B1 (FB1), which is a mycotoxin produced by Fusarium moniliforme and Fusarium rotarum, has a number of toxic effects in animals. Moldy feed containing FB1 can damage the intestine. In this study, we used intestinal porcine epithelial cells (IPEC-J2) as an in vitro model to explore the effects of FB1 on cell cycle and apoptosis. The results showed that IPEC-J2 cells treated with 10, 20, and 40 μg/mL FB1 for 48 h experienced different degrees of damage manifested as decreases in cell number and viability, as well as cell shrinkage and floating. In addition, FB1 reduced cell proliferation and the mRNA and protein expression of proliferating cell nuclear antigen (PCNA), cyclin-dependent kinase 2 (CDK2), CDK4, cyclinD1, and cyclinE1. FB1 blocked the cell cycle in the G1 phase. FB1 also induced mitochondrial pathway apoptosis, reduced mitochondrial membrane potential, and promoted mRNA and protein expression of Caspase3, Caspase9, and Bax. The findings suggest that FB1 can induce IPEC-J2 cell damage, block the cell cycle, and promote cell apoptosis.

show abstract

Fumonisin B1 exposure induces apoptosis of human kidney tubular epithelial cells through regulating PTEN/PI3K/AKT signaling pathway via disrupting lipid raft formation

Cited by 14 publications

References 26 publications

Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity

Targeted Analysis of Sphingolipids in Turkeys Fed Fusariotoxins: First Evidence of Key Changes That Could Help Explain Their Relative Resistance to Fumonisin Toxicity

Lithocholic Acid Alleviates Deoxynivalenol-Induced Lethal Cholesterol Metabolic Abnormalities in IPI-2I Cells

Effect of Fumonisin B1 on Proliferation and Apoptosis of Intestinal Porcine Epithelial Cells

Contact Info

Product

Resources

About