title: RAGE-mediated MAPK activation by food-derived AGE and non-AGE products.
abstract: Investigating the cellular effects of food compounds formed by heat treatment during processing, we recently demonstrated the expression of the receptor for advanced glycation endproducts (RAGE) and the p44/42 MAP kinase activation by casein-N(epsilon )-(carboxymethyl)lysine (casein-CML), a food-derived AGE, in the intestinal cell line Caco-2. In this work, we report a Caco-2 p44/42 MAP kinase activation by bread crust and coffee extract. After identification, quantification, and synthesis of two key compounds formed in association with the process-induced heat impact applied to bread dough and coffee beans, those compounds, namely the AGE pronyl-glycine and the non-AGE N-methylpyridinium, were also demonstrated for the first time to activate the p44/42 MAP kinase through binding to RAGE in Caco-2 cells. Blocking of RAGE by an antagonistic antibody and expression of C-terminally truncated RAGE resulted in a reduced Caco-2- and HEK-293-MAP kinase activation. These findings unequivocally point to a RAGE-mediated activating effect of chemically defined food-derived, thermally generated products, both, AGEs and non-AGEs, on cellular signal transduction pathways involved in inflammatory response and cellular proliferation.
authors.affiliation: Institut für Humanernährung und Lebensmittelkunde, Universität Kiel, Duesternbrooker Weg 17, D-24105 Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Zill
authors.forename: Stephan
authors.initials: S
authors.lastname: Bek
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Huber
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Michael
authors.initials: M
authors.lastname: Lindenmeier
authors.forename: Bernd
authors.initials: B
authors.lastname: Weigle
authors.forename: Helmut F
authors.initials: HF
authors.lastname: Erbersdobler
authors.forename: Sabine
authors.initials: S
authors.lastname: Scheidler
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Busch
authors.forename: Veronika
authors.initials: V
authors.lastname: Faist
mesh_terms: D000906:Antibodies / Q000494:pharmacology; D001939:Bread; D018938:Caco-2 Cells; D002364:Caseins / Q000494:pharmacology; D002460:Cell Line; D003069:Coffee; D004789:Enzyme Activation; D005502:Food; D017127:Glycation End Products, Advanced / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011726:Pyridinium Compounds / Q000494:pharmacology; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000276:immunology / Q000502:physiology*; D017384:Sequence Deletion; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000906:Antibodies; D002364:Caseins; D003069:Coffee; D017127:Glycation End Products, Advanced; D011726:Pyridinium Compounds; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C014677:1-methylpyridinium; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005998:Glycine