Toxalim (Research Centre in Food Toxicology), INRAE, ENVT, INP-Purpan, UPS, Université de Toulouse, Toulouse, France.
Institute of Medical Biochemistry, University of Veterinary Medicine Vienna, Veterinaerplatz 1, 1210, Vienna, Austria.
Arch Toxicol. 2022 Sep;96(9):2609-2619. doi: 10.1007/s00204-022-03318-x. Epub 2022 Jun 8.
NX is a type A trichothecene produced by Fusarium graminearum with limited information on its toxicity. NX is structurally similar to deoxynivalenol (DON), only differing by the lacking keto group at C8. Because of the structural similarity of the two toxins as well as their potential co-occurrence in food and feed, it is of interest to determine the toxicity of this new compound. In this study, we compared the protein composition of the extracellular media of pig intestinal explants (secretome) exposed to 10 µM of DON or NX for 4 h compared with controls. The combination of two complementary quantitative proteomic approaches (a gel-based and a gel-free approach) identified 18 and 23 differentially abundant proteins (DAPs) for DON and NX, respectively, compared to controls. Functional analysis suggested that, whereas DON toxicity was associated with decreased cell viability and cell destruction, NX toxicity was associated with an enrichment of mitochondrial proteins in the secretome. The presence of these proteins may be associated with the already known ability of NX to induce an intestinal inflammation. Overall, our results indicated that DON- and NX-induced changes in the extracellular proteome of intestinal explants are different. The increased leakage/secretion of mitochondrial proteins by NX may be a feature of NX toxicity.
NX 是一种由禾谷镰刀菌产生的 A 型单端孢霉烯族毒素，其毒性信息有限。NX 在结构上与脱氧雪腐镰刀菌烯醇（DON）相似，仅在 C8 位缺少酮基团。由于这两种毒素的结构相似，并且它们可能在食物和饲料中共同存在，因此确定这种新化合物的毒性很有意义。在这项研究中，我们比较了暴露于 10 µM DON 或 NX 4 小时的猪肠外植体（分泌组）细胞外培养基中的蛋白质组成与对照组。两种互补的定量蛋白质组学方法（基于凝胶和无凝胶方法）分别鉴定出 DON 和 NX 相对于对照组分别有 18 和 23 个差异丰度蛋白（DAP）。功能分析表明，虽然 DON 毒性与细胞活力下降和细胞破坏有关，但 NX 毒性与分泌组中线粒体蛋白的富集有关。这些蛋白质的存在可能与 NX 已被证明具有诱导肠道炎症的能力有关。总体而言，我们的结果表明 DON 和 NX 诱导的肠外植体细胞外蛋白质组变化不同。NX 引起的线粒体蛋白渗漏/分泌增加可能是 NX 毒性的一个特征。
