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Deoxynivalenol(DON) and related compounds target protein processing to induce immunotoxic effects in human T cells and macrophages [Zebrafish]

ABSTRACT: Deoxynivalenol (DON) is a fungal toxin mainly produced by Fusarium graminearum and Fusarium graminearum, and is present in cereal crops such as wheat, barley, oats, rye, and corn. It is widely polluted worldwide. DON and its related derivatives have a wide range of toxic effects on humans and animals. This study used zebrafish models and different cell models to verify the toxic effects of DON, and explored the mechanism of DON mediated Jurkat apoptosis and inhibition of M2 macrophage differentiation. The results indicate that the toxic effects of these fungal toxins differ significantly among various cell types. For Jurkat T cells, the IC50 values of DON, NIV, 15 Ac DON, and 3-Ac DON were 488.6 nM, 318.2 nM, 544 nM, and 6516 nM, respectively. There are significant differences in the effects on M2 polarization of macrophages, and DON, NIV, and 15 Ac DON can inhibit M2 differentiation and function of macrophages at lower dose levels. Indicating that immune toxicity is an important toxic effect of DON and its related substances. Research on its mechanism has shown that DON can target protein processing processes, interfere with the normal synthesis and folding of proteins in cells, and trigger cellular stress responses. These findings reveal the toxic effects and potential mechanisms of DON on human immune cells, providing a scientific basis for preventing and controlling DON pollution and its harm to human health.

ORGANISM(S): Danio rerio

PROVIDER: GSE284987 | GEO | 2025/12/20

REPOSITORIES: GEO

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Deoxynivalenol(DON) and related compounds target protein processing to induce immunotoxic effects in human T cells and macrophages [Jurkat]

Project description:Deoxynivalenol (DON) is a fungal toxin mainly produced by Fusarium graminearum and Fusarium graminearum, and is present in cereal crops such as wheat, barley, oats, rye, and corn. It is widely polluted worldwide. DON and its related derivatives have a wide range of toxic effects on humans and animals. This study used zebrafish models and different cell models to verify the toxic effects of DON, and explored the mechanism of DON mediated Jurkat apoptosis and inhibition of M2 macrophage differentiation. The results indicate that the toxic effects of these fungal toxins differ significantly among various cell types. For Jurkat T cells, the IC50 values of DON, NIV, 15 Ac DON, and 3-Ac DON were 488.6 nM, 318.2 nM, 544 nM, and 6516 nM, respectively. There are significant differences in the effects on M2 polarization of macrophages, and DON, NIV, and 15 Ac DON can inhibit M2 differentiation and function of macrophages at lower dose levels. Indicating that immune toxicity is an important toxic effect of DON and its related substances. Research on its mechanism has shown that DON can target protein processing processes, interfere with the normal synthesis and folding of proteins in cells, and trigger cellular stress responses. These findings reveal the toxic effects and potential mechanisms of DON on human immune cells, providing a scientific basis for preventing and controlling DON pollution and its harm to human health.

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The Transcription factor FgSfp1 orchestrates mycotoxin deoxynivalenol biosynthesis in Fusarium graminearum

Project description:Fusarium graminearum (F. graminearum) and its derivative mycotoxin deoxynivalenol (DON) are highly concerned with food security, safety and sustainability worldwide. The molecular mechanism regulates DON biosynthesis in F. graminearum remains enigmatic, despite several transcription factors (TFs) have been revealed containing regulatory functions. Here, we first characterized a zinc finger-contained TF, FgSfp1. Interestingly, contrast to the previous knowledge, all TRI-cluster genes were abnormally upregulated in ∆FgSfp1 while Tri proteins abundance rationally decreased, resulting in a 95.4% reduction of DON yield simultaneously. Further evidence determined FgSfp1 acted as a nutrient-sensing factor coordinates genetic expression efficiency through interference of ribosomal biogenesis process. Specifically, FgSfp1-depletion leads to ribosome biogenesis assembly factor (RiBi) expression attenuation along with DON precursor acetyl-CoA synthase reduction since FgSfp1 actively interacts with RNA 2’-O-methylation enzyme FgNop1 revealed by Bi-FC and subsequently influences mRNA translation capacity. In conclusion, we elucidated that the FgSfp1 orchestrates DON biosynthesis via participating RNA posttranscriptional modification for ribosomal RNA maturation, offering new insights into the DON biosynthesis regulation. Ultimately, this novel TF might be a key regulator for DON contamination control in the whole food chain.

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