摘要
The aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human neuroblastoma differentiated cells were exposed to (A) mycotoxins, (B) the digesta of mycotoxin-contaminated bread formulated with P, or (C) bread enriched with FW + P. A proteomic approach using HPLC-MS/MS-QTOF was then employed to characterize the metabolic pathways affected by the presence of these components, as well as their ability to modulate the toxic effects exacerbated by mycotoxins. Gene ontology functional analysis revealed proteins primarily associated with nucleosome structure, such as the H3-H4 tetramer, H2A-H2B dimer, and HIRA, which were overexpressed in the presence of mycotoxins and, interestingly, downregulated with the addition of the functional ingredients. Additionally, important metabolic pathways associated with the RHO GTPase family, estrogen-dependent gene expression, and androgen receptor transcription stimulated by PKN1 activation were discovered. Network interaction analysis highlighted the modulation of cytoskeletal dynamics, cell migration, and stress responses. These findings provide novel insights into the neuroprotective potential of functional food components, supporting their use in mitigating mycotoxin-induced neuronal damage and opening new avenues for dietary-based neuroprotection strategies.
摘要译文
这项工作的目的是强调发酵乳清（FW）中存在的生物活性肽的有益作用，而南瓜（P）中的类胡萝卜素对神经元水平的黄曲霉毒素B1和Ochratoxin A的促氧化作用。为此目的，将人类神经母细胞瘤分化的细胞暴露于（a）霉菌毒素，（b）用p配方的霉菌毒素毒素污染的面包的消化，或（c）面包富含FW + P的面包。一种蛋白质组学方法，一种使用HPLC-MS/MS-QTOF的蛋白质组学方法，并通过构成了这些模态，并以这些方式构成了这些概况，以这些途径来表征这些成分，这些途径是这些型号的构成，这些途径既定成分，这些途径既定为代表，并构成了这些蛋白质组学的效果。霉菌毒素加剧了毒性作用。基因本体论功能分析揭示了主要与核小体结构相关的蛋白质，例如H3-H4四聚体，H2A-H2B二聚体和HIRA，它们在霉菌毒素存在下过表达，有趣的是，功能成分的添加而下调。此外，发现了与Rho GTPase家族，雌激素依赖性基因表达和通过PKN1激活刺激的雄激素受体转录相关的重要代谢途径。网络相互作用分析强调了细胞骨架动力学，细胞迁移和应力反应的调节。这些发现为功能性食品成分的神经保护潜力提供了新的见解，支持它们在减轻霉菌毒素诱导的神经元损害的用途，并为基于饮食的神经保护策略开辟了新的途径。
Alessandra Cimbalo; Massimo Frangiamone; Lara Manyes. Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach[J]. Antioxidants, 2025,14(5): 571