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Glyoxal-Lysine Dimer, an Advanced Glycation End Product, Induces Oxidative Damage and Inflammatory Response by Interacting with RAGE
Antioxidants ( IF 6.0 ) Pub Date : 2021-09-17 , DOI: 10.3390/antiox10091486
Hee-Weon Lee 1 , Min Ji Gu 1 , Yoonsook Kim 1 , Jee-Young Lee 2 , Seungju Lee 2 , In-Wook Choi 1 , Sang Keun Ha 1, 3
Affiliation  

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.

中文翻译:

乙二醛-赖氨酸二聚体,一种高级糖化终产物,通过与 RAGE 相互作用诱导氧化损伤和炎症反应

乙二醛-赖氨酸二聚体 (GOLD) 是乙二醛 (GO) 衍生的晚期糖基化终产物 (AGE),由糖基化反应产生。在这项研究中,我们评估了 GOLD 对 SV40 MES 13 系膜细胞氧化损伤和炎症反应的影响。GOLD 显着增加了与 RAGE 的 V 型免疫球蛋白结构域的连接,RAGE 是一种特定的 AGE 受体。我们发现 GOLD 处理增加了系膜细胞中 RAGE 的表达和活性氧 (ROS) 的产生。GOLD 显着调节核因子红细胞 2 相关因子 2 (NRF2) 和乙二醛酶 1 (GLO1) 的蛋白质和 mRNA 表达。此外,线粒体退化和炎症通过 GOLD 诱导的系膜细胞氧化应激发生。GOLD 调节丝裂原活化蛋白激酶 (MAPK) 和与系膜细胞炎症机制相关的促炎细胞因子的释放。此外,GOLD 引发的氧化应激和炎症反应通过使用 RAGE siRNA 的 RAGE 抑制得到抑制。这些结果表明GOLD和RAGE的相互作用在系膜细胞的功能中起重要作用。
更新日期:2021-09-17
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