Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
Toxalim (Research Centre in Food Toxicology), Université de Toulouse, INRA, ENVT, INP-Purpan, UPS, Toulouse, France.
J Proteomics. 2018 Apr 30;178:114-122. doi: 10.1016/j.jprot.2017.12.017. Epub 2017 Dec 27.
Mycotoxins are natural food and feed contaminants that are toxic to human and animals. Proteomics is an adequate toolbox to investigate the mode of action and the effects of mycotoxins, as these toxicants often alter protein synthesis and degradation, as well as induce changes of important post-translational modifications. For instance, the contaminant deoxynivalenol induces a severe ribosomal stress that affects protein production, whereas the toxin Fumonisin B1 can alter the phosphorylation of a large number of proteins, and patulin is a potent proteotoxic molecule. The response to most mycotoxins is sex-dependent, males being generally more sensitive than females. In addition, for some toxins, the toxic effects observed were different for each sex. Nevertheless, the importance of accounting for a sex-dependent response is often overlooked in toxicology studies involving mycotoxins. Here we review the information that proteomics has provided in pre-clinical studies of mycotoxin exposure as well as the differential response of males and females to these molecules to highlight the need of including male and female individuals when evaluating the impact of mycotoxins in the cell proteome.
The current trend in mycotoxicology is the combination of several -omics techniques in order to understand the mechanism of action and effects of these toxic natural food contaminants. One of the goals of these experiments is to determine "potential biomarkers" of mycotoxicoses. Nevertheless, the strategy followed in biomarker research must take into account as many possible factors as possible in order to find robust biomarkers for differential diagnosis. Among the factors that can have an influence in the response to mycotoxins, one of the most important is sex. Traditionally, males are preferentially used in research, as they are more sensitive to mycotoxins and their response is not dependent on hormonal levels, thus less variable. However the intrinsic and hormonal differences between sexes makes that results obtained in males are often not directly transferrable to females. In this review, we want to highlight (1) that proteomics has a great potential on mycotoxin research, and (2) the need in taking into account sex differences in proteomic studies, mostly when the discovery of robust biomarkers of mycotoxins response is desired.
霉菌毒素是天然的食物和饲料污染物，对人类和动物有毒。蛋白质组学是一种充分的工具盒，可以研究霉菌毒素的作用模式和影响，因为这些毒素经常改变蛋白质的合成和降解，并诱导重要的翻译后修饰的变化。例如，污染物脱氧雪腐镰刀菌烯醇诱导严重的核糖体应激，影响蛋白质的产生，而毒素伏马菌素 B1 可以改变大量蛋白质的磷酸化，棒曲霉素是一种有效的蛋白毒性分子。大多数霉菌毒素的反应是性别依赖性的，男性通常比女性更敏感。此外，对于一些毒素，观察到的毒性作用因性别而异。然而，在涉及霉菌毒素的毒理学研究中，经常忽略了考虑性别依赖性反应的重要性。在这里，我们综述了蛋白质组学在霉菌毒素暴露的临床前研究中提供的信息，以及男性和女性对这些分子的不同反应，以强调在评估霉菌毒素对细胞蛋白质组的影响时需要包括男性和女性个体。
霉菌毒素毒理学的当前趋势是将几种组学技术结合起来，以了解这些有毒天然食物污染物的作用机制和影响。这些实验的目标之一是确定“霉菌毒素病的潜在生物标志物”。然而，生物标志物研究中所遵循的策略必须考虑到尽可能多的可能因素，以便为鉴别诊断找到稳健的生物标志物。在可能影响霉菌毒素反应的因素中，最重要的因素之一是性别。传统上，男性在研究中更受青睐，因为他们对霉菌毒素更敏感，而且他们的反应不受激素水平的影响，因此更具可变性。然而，由于内在和激素的性别差异，在男性中获得的结果往往不能直接转移到女性身上。在这篇综述中，我们想强调（1）蛋白质组学在霉菌毒素研究中有很大的潜力，（2）在蛋白质组学研究中需要考虑性别差异，尤其是当需要发现霉菌毒素反应的稳健生物标志物时。
