Advanced glycation endproducts interfere with adhesion and neurite outgrowth

PLoS One. 2014 Nov 11;9(11):e112115. doi: 10.1371/journal.pone.0112115. eCollection 2014.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Adhesion / drug effects
  • Cell Adhesion / physiology*
  • Collagen / metabolism
  • Glycation End Products, Advanced / metabolism*
  • Laminin / metabolism
  • Nerve Growth Factor / pharmacology
  • Neurites / drug effects
  • Neurites / metabolism*
  • PC12 Cells
  • Rats

Substances

  • Glycation End Products, Advanced
  • Laminin
  • Collagen
  • Nerve Growth Factor

Grant support

The authors received funding by the Medical Faculty of the Martin-Luther-University (Roux-TIF). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.