RAGE-mediated MAPK activation by food-derived AGE and non-AGE products.
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.
Zill
Holger
H
Institut für Humanernährung und Lebensmittelkunde, Universität Kiel, Duesternbrooker Weg 17, D-24105 Kiel, Germany.
Bek
Stephan
S
Hofmann
Thomas
T
Huber
Jochen
J
Frank
Oliver
O
Lindenmeier
Michael
M
Weigle
Bernd
B
Erbersdobler
Helmut F
HF
Scheidler
Sabine
S
Busch
Andreas E
AE
Faist
Veronika
V
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
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