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

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.