title: Dietary bread crust advanced glycation end products bind to the receptor for AGEs in HEK-293 kidney cells but are rapidly excreted after oral administration to healthy and subtotally nephrectomized rats.
abstract: In renal HEK-293 cells, the dietary Maillard reaction compounds casein-linked Nepsilon-carboxymethyllysine (CML), CML, bread crust (BC), and pronyl-glycine (a key compound formed in association with the process-induced heat impact applied to bread dough) all showed activation of p38-MAP kinase. Expression of the C-terminus truncated receptor for advanced glycation end products (RAGE) resulted in a reduction of HEK-293-MAP kinase activation. As these findings suggested a RAGE-mediated activating effect of CML, BC, and pronyl-glycine on kidney cellular signal transduction pathways, an in vivo study was performed. Male Wistar rats were subjected to a sham operation (CTRL, n = 20) or to 5/6 nephrectomy (NX, n = 20). Both groups were randomized into two subgroups and fed 20 g of a diet containing either 25% by weight BC or wheat starch (WS). GC-MS analyses of CML, carboxyethyllysine (CEL), and pentosidine revealed increased levels of CML and CEL in the liver but decreased levels of CML in the kidneys of CTRL and NX rats fed the BC diet compared to those on the WS diet. However, urinary levels of CML were also elevated in the CTRL and NX rats on the BC diet, pointing to enhanced excretion of AGEs after BC administration. Although renal insufficiency in the NX rats was reflected by proteinuria, the renal handling of CML and, presumably, other AGEs was not impaired.
authors.affiliation: German Research Center for Food Chemistry, Lichtenbergstrasse 4, 85748 Garching, Germany. veronika.somoza@lrz.tum.de
authors.forename: Veronika
authors.initials: V
authors.lastname: Somoza
authors.forename: Michael
authors.initials: M
authors.lastname: Lindenmeier
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Frank
authors.forename: Helmut F
authors.initials: HF
authors.lastname: Erbersdobler
authors.forename: John W
authors.initials: JW
authors.lastname: Baynes
authors.forename: Suzanne R
authors.initials: SR
authors.lastname: Thorpe
authors.forename: August
authors.initials: A
authors.lastname: Heidland
authors.forename: Holger
authors.initials: H
authors.lastname: Zill
authors.forename: Stephan
authors.initials: S
authors.lastname: Bek
authors.forename: Jochen
authors.initials: J
authors.lastname: Huber
authors.forename: Thomas
authors.initials: T
authors.lastname: Weigle
authors.forename: Sabine
authors.initials: S
authors.lastname: Scheidler
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Busch
authors.forename: Katarína
authors.initials: K
authors.lastname: Sebeková
mesh_terms: D000818:Animals; D001939:Bread; D002460:Cell Line; D004032:Diet; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism*; D012016:Reference Values; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D048051:p38 Mitogen-Activated Protein Kinases