Methylglyoxal-derived hydroimidazolone-1 evokes inflammatory reactions in endothelial cells via an interaction with receptor for advanced glycation end products

Diab Vasc Dis Res. 2017 Sep;14(5):450-453. doi: 10.1177/1479164117715855. Epub 2017 Jun 20.

Abstract

Objective: Glyceraldehyde-derived advanced glycation end products contribute to vascular inflammation in diabetes. However, what advanced glycation end product structure could evoke inflammatory reactions remains unknown. We examined whether and how methylglyoxal-derived hydroimidazolone 1, one of the advanced glycation end products formed from glyceraldehyde, elicits inflammatory reactions in human umbilical vein endothelial cells.

Materials and methods: Glyceraldehyde-advanced glycation end products-aptamer was prepared using a systemic evolution of ligands by exponential enrichment. The binding affinities of methylglyoxal-derived hydroimidazolone 1 to receptor for advanced glycation end products or advanced glycation end product-aptamer were measured with a quartz crystal microbalance. Intracellular reactive oxygen species generation and THP-1 cell adhesion were evaluated using fluorescent probes. Gene expression was analysed by reverse transcription polymerase chain reaction.

Results: Methylglyoxal-derived hydroimidazolone 1 bound to receptor for advanced glycation end products and advanced glycation end product-aptamer with a dissociation constant ( Kd) of 56.7 µM and 1.51 mM, respectively. Methylglyoxal-derived hydroimidazolone 1 at 100 µg/mL significantly increased reactive oxygen species generation in human umbilical vein endothelial cells, which were attenuated by anti-receptor for advanced glycation end products antibody or advanced glycation end product-aptamer. In all, 100 µg/mL methylglyoxal-derived hydroimidazolone 1 significantly increased receptor for advanced glycation end products and intercellular adhesion molecule-1 messenger RNA levels in, and THP-1 cell adhesion to, human umbilical vein endothelial cells, all of which were blocked by anti-receptor for advanced glycation end products antibody.

Conclusion: Our present results indicate that methylglyoxal-derived hydroimidazolone 1 evokes inflammatory reactions in human umbilical vein endothelial cells via receptor for advanced glycation end products, although apparently limited to supraphysiological levels of methylglyoxal-derived hydroimidazolone 1. Methylglyoxal-derived hydroimidazolone 1 is a distinct advanced glycation end product structure that could mediate harmful effects of methylglyoxal and glyceraldehyde-mediated glycation processes.

Keywords: Methylglyoxal-derived hydroimidazolone 1; endothelial cells; inflammation; receptor for advanced glycation end products.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Line
  • Glycation End Products, Advanced / metabolism
  • Glycation End Products, Advanced / toxicity*
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / immunology
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Imidazoles / metabolism
  • Imidazoles / toxicity*
  • Inflammation / chemically induced*
  • Inflammation / immunology
  • Inflammation / metabolism
  • Inflammation Mediators / metabolism*
  • Leukocytes / drug effects
  • Leukocytes / immunology
  • Leukocytes / metabolism
  • Protein Binding
  • Pyruvaldehyde / metabolism
  • Pyruvaldehyde / toxicity*
  • Reactive Oxygen Species / metabolism
  • Receptor for Advanced Glycation End Products / agonists*
  • Receptor for Advanced Glycation End Products / metabolism
  • Signal Transduction / drug effects
  • Time Factors

Substances

  • AGER protein, human
  • Glycation End Products, Advanced
  • Imidazoles
  • Inflammation Mediators
  • Reactive Oxygen Species
  • Receptor for Advanced Glycation End Products
  • imidazolone
  • Pyruvaldehyde