Department for Cardiac Surgery, University Hospital Halle (Saale), Martin-Luther University Halle-Wittenberg, 06120 Halle (Saale), Germany.
Center for Medical Basic Research, Martin-Luther-University Halle-Wittenberg, 06120 Halle (Saale), Germany.
Nutrients. 2021 Oct 29;13(11):3874. doi: 10.3390/nu13113874.
Advanced glycation end products (AGEs) result from a non-enzymatic reaction of proteins with reactive carbohydrates. Heat-processed food, such as bread, contains high amounts of AGEs. The activation of the NF-κB signaling pathway by bread crust extract (BCE) is well understood. However, it is largely unknown whether NRF2, the master regulator of oxidative stress resistance in mammalian cells, is affected by BCE. We have investigated the molecular mechanisms by which BCE induces antioxidant gene expression in cellular models. Our data showed that soluble extracts from bread crust are capable of stimulating the NRF2 signaling pathway. Furthermore, NRF2 pathway activation was confirmed by microarray and reporter-cell analyses. QRT-PCR measurements and Western blot analyses indicated an induction of antioxidative genes such as HMOX1, GCLM and NQO1 upon BCE treatment. Moreover, BCE pretreated cells had a survival advantage compared to control cells when exposed to oxidative stress. BCE induces phosphorylation of AKT and ERK kinase in EA.hy926 cells. By mass spectrometry, several new, potentially active modifications in BCE were identified. Our findings indicate that BCE activates NRF2-dependent antioxidant gene expression, thus provoking a protection mechanism against oxidative stress-mediated tissue injury. Hence, BCE can be considered as functional food with antioxidative and cardioprotective potential.
糖基化终产物（AGEs）是蛋白质与反应性碳水化合物发生非酶反应的结果。经过热加工的食物，如面包，含有大量的 AGEs。面包皮提取物（BCE）激活 NF-κB 信号通路的机制已经得到很好的理解。然而，BCE 是否会影响细胞内氧化应激抵抗的主调控因子 NRF2，在很大程度上还不清楚。我们研究了 BCE 诱导细胞模型中抗氧化基因表达的分子机制。我们的数据表明，面包皮的可溶性提取物能够刺激 NRF2 信号通路。此外，通过微阵列和报告细胞分析证实了 NRF2 通路的激活。QRT-PCR 测量和 Western blot 分析表明，BCE 处理后诱导了抗氧化基因如 HMOX1、GCLM 和 NQO1 的表达。此外，与对照细胞相比，BCE 预处理的细胞在暴露于氧化应激时具有生存优势。BCE 在 EA.hy926 细胞中诱导 AKT 和 ERK 激酶的磷酸化。通过质谱分析，在 BCE 中鉴定出几种新的、潜在活跃的修饰。我们的研究结果表明，BCE 激活了 NRF2 依赖性抗氧化基因表达，从而引发了一种针对氧化应激介导的组织损伤的保护机制。因此，BCE 可以被认为是具有抗氧化和心脏保护潜力的功能性食品。
