Advanced glycation endproducts interfere with adhesion and neurite outgrowth

• Published in: PloS one 2014-11, Vol.9 (11), p.e112115-e112115
• Main Authors: Bennmann, Dorit, Horstkorte, Rüdiger, Hofmann, Britt, Jacobs, Kathleen, Navarrete-Santos, Alexander, Simm, Andreas, Bork, Kaya, Gnanapragassam, Vinayaga S
• Format: Article
• Language: English
• Subjects: Adhesion; Advanced glycosylation end products; Age; Aging; Amino acids; Amino groups; Animals; Apoptosis - drug effects; Apoptosis - physiology; Axonogenesis; Biology and Life Sciences; Biomarkers; Blood levels; Carbonyl compounds; Carbonyls; Cell adhesion & migration; Cell Adhesion - drug effects; Cell Adhesion - physiology; Cell culture; Chemical reactions; Collagen; Collagen - metabolism; Dehydration; Diabetes mellitus; Diabetics; Disease; Enzymes; Extracellular matrix; Fructose; Glucose; Glycation End Products, Advanced - metabolism; Glycosylation; Growth factors; Kinases; Laminin; Laminin - metabolism; Life sciences; Metabolism; Metabolites; Monosaccharides; Nerve growth factor; Nerve Growth Factor - pharmacology; Neurites - drug effects; Neurites - metabolism; Neuroplasticity; Oxidation; Pathogenesis; PC12 Cells; Pheochromocytoma cells; Phosphorylation; Physiological aspects; Plasticity (neural); Proteins; Pyruvaldehyde; Rats; Rodents; Signal transduction; Tissues
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0112115

Advanced glycation endproducts (AGEs) represent a non-enzymatic posttranslational protein modification. AGEs are generated by a series of chemical reactions of free reducing monosaccharides, such as glucose, fructose or metabolites of the monosaccharide metabolism with amino groups of proteins. After oxidation, dehydration and condensation, stable AGE-modifications are formed. AGE-modified proteins accumulate in all cells and tissues as a normal feature of ageing and correlate with the glucose concentration in the blood. AGEs are increased in diabetic patients and play a significant role in the pathogenesis of most age-related neural disorders, such as Alzheimer's disease. We examined the role of AGEs on neurite outgrowth of PC12 cells. We induced the formation of AGEs using the reactive carbonyl compound methylglyoxal (MGO) as a physiological metabolite of glucose. We found that AGE-modification of laminin or collagen interfered with adhesion but not with neurite outgrowth of PC12 cells. Furthermore, the AGE-modification of PC12 cell proteins reduced NGF-induced neurite outgrowth. In conclusion, our data show that AGEs negatively influence neural plasticity.