Glyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Oxidative Damage and Inflammatory Response by Interacting with RAGE

The glyoxal-lysine dimer (GOLD), which is a glyoxal (GO)-derived advanced glycation end product (AGE), is produced by the glycation reaction. In this study, we evaluated the effect of GOLD on the oxidative damage and inflammatory response in SV40 MES 13 mesangial cells. GOLD significantly increased the linkage with the V-type immunoglobulin domain of RAGE, a specific receptor of AGE. We found that GOLD treatment increased RAGE expression and reactive oxygen species (ROS) production in mesangial cells. GOLD remarkably regulated the protein and mRNA expression of nuclear factor erythroid 2-related factor 2 (NRF2) and glyoxalase 1 (GLO1). In addition, mitochondrial deterioration and inflammation occurred via GOLD-induced oxidative stress in mesangial cells. GOLD regulated the mitogen-activated protein kinase (MAPK) and the release of proinflammatory cytokines associated with the inflammatory mechanism of mesangial cells. Furthermore, oxidative stress and inflammatory responses triggered by GOLD were suppressed through RAGE inhibition using RAGE siRNA. These results demonstrate that the interaction of GOLD and RAGE plays an important role in the function of mesangial cells.

Automated summary

This study evaluated the impact of glyoxal-lysine dimer (GOLD) on oxidative damage and inflammatory response in SV40 MES 13 mesangial cells. GOLD increased RAGE expression, reactive oxygen species production, and regulated NRF2 and GLO1 expression. Additionally, GOLD induced mitochondrial deterioration and inflammation through oxidative stress, and regulated MAPK and proinflammatory cytokines release. Inhibition of RAGE using RAGE siRNA suppressed the oxidative stress and inflammatory responses triggered by GOLD, highlighting the importance of the interaction between GOLD and RAGE in mesangial cell function.