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Advanced glycation end products (AGEs) that arise from the reaction of sugars with protein side chains and the terminal amino group are supposed to be involved in the pathogenesis of several diseases and therefore the effects of AGEs on cells are the objective of numerous investigations. The effects of AGEs on cells are commonly assumed to be transduced via the receptor for AGEs (RAGE) but there are also other receptors known to interact with AGEs and they are likely to be involved in signal transduction. The primary cellular effect of AGEs on cultured cells was found to be the formation of reactive oxygen species (ROS). For the present study one murine and three human cell lines were used. The effects of a set of different highly modified AGEs and AGE-like compounds derived from the incubation of different modifiers with BSA were tested for their effects on these cells. Almost all AGEs tested induced the production of reactive oxygen species (ROS) in the different cell lines although the intensity of the detected signals varied considerably between the cell lines and are strongly dependent on the AGE used for cell activation. The most highly modified BSA-species were shown to inhibit cell growth in all cell lines, whereas a moderately modified glucose derived BSA-AGE and BSA-GA(red) did not show any inhibitory effect on cell growth even when a high ROS formation was detected.

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Advanced glycation endproducts (AGEs) arise from the reaction of sugars with side chains and the N-terminus of proteins and are thought to be involved in the pathogenesis of several diseases by inducing oxidative stress, inflammation and cell death presumably mediated through activation of the receptor of AGE (RAGE). To address the question whether the cell damaging effect of AGE depends on the degree of its protein glycation, differential modified AGEs derived from incubating human serum albumin with increasing concentrations of methyl glyoxal were tested on cell viability, reactive oxygen species (ROS) formation, intracellular ATP levels, and activation of caspases 3/7 in two human glial cell lines, which were used as a model for human glia cells. All AGEs tested, regardless of their degree of modification, were found to induce ROS formation in both microglial (CHME-5) and astroglial cells (U373 MG), while only highly modified AGEs were able to decrease the cell viability and to induce apoptosis. This indicates that apoptotic events may be involved in the change of physiological parameters.