Zill Holger, Bek Stephan, Hofmann Thomas, Huber Jochen, Frank Oliver, Lindenmeier Michael, Weigle Bernd, Erbersdobler Helmut F, Scheidler Sabine, Busch Andreas E, Faist Veronika
Institut für Humanernährung und Lebensmittelkunde, Universität Kiel, Duesternbrooker Weg 17, D-24105 Kiel, Germany.
Biochem Biophys Res Commun. 2003 Jan 10;300(2):311-5. doi: 10.1016/s0006-291x(02)02856-5.
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.
在研究加工过程中热处理形成的食品化合物的细胞效应时，我们最近证明了在肠细胞系Caco-2中，食品来源的晚期糖基化终产物（AGE）——酪蛋白-N(ε)-(羧甲基)赖氨酸（酪蛋白-CML）可诱导晚期糖基化终产物受体（RAGE）的表达以及p44/42丝裂原活化蛋白激酶的激活。在这项研究中，我们报告了面包皮和咖啡提取物可激活Caco-2细胞中的p44/42丝裂原活化蛋白激酶。在对面包面团和咖啡豆施加加工过程中诱导的热影响所形成的两种关键化合物进行鉴定、定量和合成后，首次证明这些化合物，即AGE丙酰甘氨酸和非AGE N-甲基吡啶鎓，通过与Caco-2细胞中的RAGE结合来激活p44/42丝裂原活化蛋白激酶。用拮抗抗体阻断RAGE以及C末端截短的RAGE的表达导致Caco-2细胞和HEK-293细胞中丝裂原活化蛋白激酶的激活减少。这些发现明确指出，化学定义的食品来源的热生成产物，包括AGEs和非AGEs，对参与炎症反应和细胞增殖的细胞信号转导途径具有RAGE介导的激活作用。
