Glycation and the accumulation of advanced glycation end products (AGEs) are known to occur during normal aging but also in the progression of several diseases, such as diabetes. Diabetes type II and aging both lead to impaired wound healing. It has been demonstrated that macrophages play an important role in impaired wound healing, however, the underlying causes remain unknown. Elevated blood glucose levels as well as elevated methylglyoxal (MGO) levels in diabetic patients result in glycation and increase of AGEs. We used MGO to investigate the influence of glycation and AGEs on macrophages. We could show that glycation, but not treatment with AGE-modified serum proteins, increased expression of pro-inflammatory cytokines interleukin 1β (IL-1β) and IL-8 but also affected IL-10 and TNF-α expression, resulting in increased inflammation. At the same time, glycation reduced phagocytic efficiency and led to impaired clearance rates of invading microbes and cellular debris. Our data suggest that glycation contributes to changes of macrophage activity and cytokine expression and therefore could support the understanding of disturbed wound healing during aging and diabetes.
The balance between protein synthesis and degradation regulates the amount of expressed proteins. This protein turnover is usually quantified as the protein half-life time. Several studies suggest that protein degradation decreases with age and leads to increased deposits of damaged and non-functional proteins. Glycation is an age-dependent, non-enzymatic process leading to posttranslational modifications, so-called advanced glycation endproducts (AGE), which usually damage proteins and lead to protein aggregation. AGE are formed by the Maillard reaction, where carbonyls of carbohydrates or metabolites react with amino groups of proteins. In this study, we quantified the half-life time of two important receptors of the immunoglobulin superfamily, the neural cell adhesion molecule (NCAM) and the receptor for advanced glycation end products (RAGE) before and after glycation. We found, that in two rat PC12 cell lines glycation leads to increased turnover, meaning that glycated, AGE-modified proteins are degraded faster than non-glycated proteins. NCAM is the most prominent carrier of a unique enzymatic posttranslational modification, the polysialylation. Using two PC12 cell lines (a non-polysialylated and a polysialylated one), we could additionally demonstrate, that polysialylation of NCAM has an impact on its turnover and that it significantly increases its half-life time.
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