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RAGE Expression and AGE-Induced MAP Kinase Activation in Caco-2 Cells

https://doi.org/10.1006/bbrc.2001.5901Get rights and content

Abstract

RAGE (receptor for advanced glycation end products) is a multiligand cell surface molecule of the immunoglobulin superfamily. It was originally described as a receptor for protein adducts formed by glycoxidation (AGEs) that accumulate in diseases such as diabetes and renal failure. Performing RT-PCR and Western blot analysis we intended to determine RAGE expression in the human colon adenocarcinoma cell line Caco-2. Moreover, Caco-2 cells were incubated in the presence of AGEs. Since RAGE ligation triggers the p21ras signal transduction pathway the activation state of p44/42 (ERK1/2) MAP kinases was determined. Here we demonstrate for the first time that Caco-2 cells express RAGE and that administration of the food-derived casein-linked AGE Nϵ-(carboxymethyl)lysine (Cas-CML) results in Caco-2 p44/42 (ERK1/2) MAP kinase activation.

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    Among these modified proteins, annexin I was overexpressed in HER2-negative/estrogen receptor (ER)-positive invasive ductal carcinoma in an earlier study [36]. MAPK was also found to be activated by the AGE–RAGE interaction to induce colon adenocarcinoma [37]. AGEs were also found to promote proliferation and metastasis in breast cancer cell lines.

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To whom correspondence and reprint requests should be addressed at Institute of Human Nutrition and Food Science, University of Kiel, Duesternbrooker Weg 17, D-24105 Kiel, Germany. Fax: +49-431-880-5679. E-mail: [email protected].

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