A. Simm, S. Daoud, J. Wagner, C. Casselmann, R.-E. Silber

Advanced glycation endproducts (AGEs) are the result of a non-enzymatic reaction of reducing sugars and primary amino-groups of proteins (Maillard reaction). They accumulate in various tissues in the course of ageing and induce protein crosslinks as well as oxidative stress (radicals) within cells and tissues.

AGEs activate cardiac fibroblasts and stimulate the induction of signalling pathways, for example, the ERK and the NF-kB pathway. Thereafter, the expression and activation of MMP-2, MMP-9 and MMP-13 are induced, which may be responsible for tissue remodelling. In addition, AGEs as well as their receptor RAGE are correlated with an impaired left ventricular function. These data support a pathophysiological role of AGEs/RAGE during aging. In contrast, we detected a reduced expression of RAGE in bronchial carcinoma tissue in comparison to normal lung. This observation was also true for heart, colon and thyroid tumour tissue. Overexpression of RAGE in a bronchial carcinoma cell line H358 led to a reduced tumour growth in vitro.

Therefore, RAGE seems to be a new pleiotropic antagonistic gene which is needed during youth (prevention of tumour growth) but has pathophysiological effects during ageing (arteriosclerosis, Alzheimers disease, cardiac dysfunction).

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oxidative stress