Advanced glycation endproducts interfere with adhesion and neurite outgrowth.
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.
Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Dorit
D
Bennmann
Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Rüdiger
R
Horstkorte
Department of Cardiothoracic Surgery, University Hospital, Halle (Saale), Germany.
Britt
B
Hofmann
Department of Cardiothoracic Surgery, University Hospital, Halle (Saale), Germany.
Kathleen
K
Jacobs
Department of Cardiothoracic Surgery, University Hospital, Halle (Saale), Germany.
Alexander
A
Navarrete-Santos
Department of Cardiothoracic Surgery, University Hospital, Halle (Saale), Germany.
Andreas
A
Simm
Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Kaya
K
Bork
Institute for Physiological Chemistry, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany.
Vinayaga S
VS
Gnanapragassam
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology*; D003094:Collagen / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D007797:Laminin / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats
D017127:Glycation End Products, Advanced; D007797:Laminin; D003094:Collagen; D020932:Nerve Growth Factor