Methylglyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Inflammation via Interaction with RAGE in Mesangial Cells.

Abstract

INTRODUCTION:

Advanced glycation end products (AGEs) and receptor of advanced glycation end products (RAGE) mediate renal function during diabetic and non-diabetic nephropathy development. Methylglyoxal-lysine dimer (MOLD), a typical toxic advanced glycation end product (TAGE), contributes to inflammatory responses during renal diseases. This study determines the effect of MOLD on inflammatory responses in mouse mesangial cells.

METHODS AND RESULTS:

The murine mesangial cell line SV40 MES 13 is used to assess nuclear factor-kappa B (NF-κB) expression, reactive oxygen species (ROS) production, and mitochondria labeling. The interaction model between RAGE and MOLD is also determined. MOLD treatment of mesangial cells markedly increases RAGE expression and the linkage with V-type Ig domain of RAGE. MOLD induces ROS production and mitochondrial dysfunction. MOLD activates phosphatidylinositol 3-kinase-protein kinase B (PI3KB) and NF-κB signaling pathways. It is confirmed that these changes are reversed when ROS is suppressed. These effects may be regulated through mitogen-activated protein kinases and pro-inflammatory cytokines in circulatory inflammation responses.

CONCLUSION:

MOLD plays a major role in nephropathy via ROS production and mitochondrial dysfunction through direct association with RAGE. Further, the NF-kB and PI3K/AKT signaling pathways triggered by ROS mediate the inflammatory response to exacerbate MOLD-induced damages in inflammation-related diabetic and non-diabetic renal diseases.

• Authors: Hee-Weon Lee, Min Ji Gu, Jee-Young Lee, Seungju Lee, Yoonsook Kim, Sang Keun Ha
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 65 Issue 13 Pg. e2000799 (07 2021) ISSN: 1613-4133 [Electronic] Germany
• PMID: 33890707 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 Wiley-VCH GmbH.

Chemical References

• Glycation End Products, Advanced
• NF-kappa B
• Reactive Oxygen Species
• Pyruvaldehyde
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinases
• Lysine

Topics

• Animals
• Cell Line
• Glycation End Products, Advanced (adverse effects)
• Inflammation (chemically induced)
• Lysine (adverse effects)
• Mesangial Cells (drug effects, metabolism)
• Mice
• Mitochondria (drug effects)
• Mitogen-Activated Protein Kinases (metabolism)
• NF-kappa B (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Pyruvaldehyde (adverse effects)
• Reactive Oxygen Species (metabolism)
• Signal Transduction