Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstr. 19, 91052, Erlangen, Germany.
Amino Acids. 2013 Jun;44(6):1427-39. doi: 10.1007/s00726-012-1222-1. Epub 2012 Jan 25.
In addition to direct antioxidative effects, Maillard reaction products (MRPs) could increase the antioxidative capacity of cells through the induction of cytoprotective enzymes. Since many of those enzymes are regulated by the transcription factor Nrf2, the effect of MRPs on nuclear translocation of Nrf2 in macrophages and Caco-2 cells was investigated. Stimulation of both cell types by MRPs showed a concentration-dependent significant increase in nuclear translocation of Nrf2 up to fivefold after short-term (2 h) and up to 50-fold after long-term treatment (24 h). In intact human gut tissue, nuclear translocation of Nrf2 was significantly twofold increased after short-term incubation. To study the activation mechanisms, macrophages and Caco-2 cells were stimulated with MRPs in the presence of catalase, which significantly suppressed Nrf2 activation. Thus, activation was related to extracellular H2O2 continuously formed from MRPs. Short-term incubation with coffee, a MRP-rich beverage, led to a trend towards Nrf2 activation in macrophages, but not in Caco-2 cells or intact human gut tissue. Long-term incubation with coffee (1-4 mg/mL) significantly increased nuclear Nrf2 up to 17-fold. Since raw coffee was inactive under the tested conditions, the effect was related to roasting products. Coffee-induced Nrf2 translocation was, however, only slightly reversed by catalase. Therefore, the Nrf2 activity of coffee can only partially be explained by MRP-induced, H2O2-dependent mechanisms. Thus, it can be concluded that MRPs may increase the antioxidative capacity inside the cell by inducing Nrf2-regulated signalling pathways not only in different cell types, but also in intact gut tissue.
除了直接的抗氧化作用外，美拉德反应产物（MRP）还可以通过诱导细胞保护性酶来增加细胞的抗氧化能力。由于许多这些酶受转录因子 Nrf2 的调节，因此研究了 MRP 对巨噬细胞和 Caco-2 细胞中 Nrf2 的核易位的影响。MRP 刺激两种细胞类型均表现出浓度依赖性的 Nrf2 核易位显著增加，短期（2 h）处理后增加了五倍，长期（24 h）处理后增加了 50 倍。在完整的人肠道组织中，短期孵育后 Nrf2 的核易位明显增加了两倍。为了研究激活机制，用 MRP 刺激巨噬细胞和 Caco-2 细胞，并用 catalase 显著抑制 Nrf2 激活。因此，激活与从 MRP 连续形成的细胞外 H2O2 有关。用富含 MRP 的饮料咖啡短期孵育会导致巨噬细胞中 Nrf2 激活的趋势，但在 Caco-2 细胞或完整的人肠道组织中则没有。用咖啡（1-4 mg/mL）长期孵育可使核 Nrf2 增加高达 17 倍。由于在测试条件下生咖啡没有活性，因此该作用与烘焙产物有关。但是，咖啡诱导的 Nrf2 易位仅被 catalase 轻微逆转。因此，咖啡引起的 Nrf2 活性只能部分通过 MRP 诱导的 H2O2 依赖性机制来解释。因此，可以得出结论，MRP 不仅可以通过诱导 Nrf2 调节的信号通路来增加不同细胞类型以及完整肠道组织内的细胞抗氧化能力，还可以增加细胞内的抗氧化能力。
