title: Activation of the transcription factor Nrf2 in macrophages, Caco-2 cells and intact human gut tissue by Maillard reaction products and coffee.
abstract: 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.
authors.affiliation: Department of Chemistry and Pharmacy, Food Chemistry, Emil Fischer Center, Friedrich-Alexander University, Schuhstr. 19, 91052, Erlangen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Sauer
authors.forename: Martin
authors.initials: M
authors.lastname: Raithel
authors.forename: Jürgen
authors.initials: J
authors.lastname: Kressel
authors.forename: Gerald
authors.initials: G
authors.lastname: Münch
authors.forename: Monika
authors.initials: M
authors.lastname: Pischetsrieder
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D018938:Caco-2 Cells / Q000187:drug effects / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D002478:Cells, Cultured; D003069:Coffee; D004305:Dose-Response Relationship, Drug; D005511:Food Handling / Q000379:methods; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D015416:Maillard Reaction; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D051381:Rats
chemical_list: D000975:Antioxidants; D003069:Coffee; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; C495637:Nfe2l2 protein, rat; D006861:Hydrogen Peroxide; D002374:Catalase