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Advanced glycation end product recognition by the receptor for AGEs.

ABSTRACT: Nonenzymatic protein glycation results in the formation of advanced glycation end products (AGEs) that are implicated in the pathology of diabetes, chronic inflammation, Alzheimer's disease, and cancer. AGEs mediate their effects primarily through a receptor-dependent pathway in which AGEs bind to a specific cell surface associated receptor, the Receptor for AGEs (RAGE). N(?)-carboxy-methyl-lysine (CML) and N(?)-carboxy-ethyl-lysine (CEL), constitute two of the major AGE structures found in tissue and blood plasma, and are physiological ligands of RAGE. The solution structure of a CEL-containing peptide-RAGE V domain complex reveals that the carboxyethyl moiety fits inside a positively charged cavity of the V domain. Peptide backbone atoms make specific contacts with the V domain. The geometry of the bound CEL peptide is compatible with many CML (CEL)-modified sites found in plasma proteins. The structure explains how such patterned ligands as CML (CEL)-proteins bind to RAGE and contribute to RAGE signaling.

SUBMITTER: Xue J

PROVIDER: S-EPMC3150472 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Advanced glycation end product recognition by the receptor for AGEs.

Xue Jing J Rai Vivek V Singer David D Chabierski Stefan S Xie Jingjing J Reverdatto Sergey S Burz David S DS Schmidt Ann Marie AM Hoffmann Ralf R Shekhtman Alexander A

Structure (London, England : 1993) 20110501 5

Nonenzymatic protein glycation results in the formation of advanced glycation end products (AGEs) that are implicated in the pathology of diabetes, chronic inflammation, Alzheimer's disease, and cancer. AGEs mediate their effects primarily through a receptor-dependent pathway in which AGEs bind to a specific cell surface associated receptor, the Receptor for AGEs (RAGE). N(ɛ)-carboxy-methyl-lysine (CML) and N(ɛ)-carboxy-ethyl-lysine (CEL), constitute two of the major AGE structures found in tiss ...[more]

PMID: 21565706

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Project description:BackgroundAdvanced glycation end products (AGEs) promote adverse health effects and may contribute to the multi-system functional decline observed in aging. Diet is a major source of AGEs, and foods high in protein may increase circulating AGE concentrations. However, epidemiological evidence that high-protein diets increase AGEs is lacking.ObjectivesWe examined whether dietary protein intake was associated with serum concentrations of the major AGE carboxymethyl-lysine (CML) and the soluble receptor for AGEs (sRAGE) in 2439 participants from the Health, Aging, and Body Composition study (mean age, 73.6 ± 2.9 y; 52% female; 37% black).MethodsCML and sRAGE were measured by ELISA, and the CML/sRAGE ratio was calculated. Protein intake was estimated using an interviewer-administered FFQ and categorized based on current recommendations for older adults: <0.8 g/kg/d (n = 1077), 0.8 to <1.2 g/kg/d (n = 922), and ≥1.2 g/kg/d (n = 440). Associations between protein intake and AGE-RAGE biomarkers were examined using linear regression models adjusted for demographics, height, lifestyle behaviors, prevalent disease, cognitive function, inflammation, and other dietary factors.ResultsCML concentrations were higher in individuals with higher total protein intake (adjusted least squares mean ± SE: <0.8 g/kg/d, 829 ± 17 ng/ml; 0.8 to <1.2 g/kg/d, 860 ± 15 ng/ml; ≥1.2 g/kg/d, 919 ± 23 ng/ml; P for trend = 0.001), as were sRAGE concentrations (<0.8 g/kg/d, 1412 ± 34 pg/ml; 0.8 to <1.2 g/kg/d, 1479 ± 31 pg/ml; ≥1.2 g/kg/d, 1574 ± 47 pg/ml; P for trend < 0.0001). Every 0.1 g/kg/d increment in total protein intake was associated with a 13.3 ± 3.0 ng/ml increment in CML and a 22.1 ± 6.0 pg/ml increment in sRAGE (P < 0.0001 for both). Higher CML and sRAGE concentrations were also associated with higher intakes of both animal and vegetable protein (all P values ≤ 0.01). There were no significant associations with the CML/sRAGE ratio.ConclusionsHigher dietary protein intake was associated with higher CML and sRAGE concentrations in older adults; however, the CML/sRAGE ratio remained similar across groups.

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Advanced glycation end product recognition by the receptor for AGEs.

Publications

Advanced glycation end product recognition by the receptor for AGEs.

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