Murakami Yoto, Fujino Takayuki, Hasegawa Toshiki, Kurachi Ryotaro, Miura Aya, Daikoh Takumi, Usui Teruyuki, Hayase Fumitaka, Watanabe Hirohito
a Department of Agriculture , Meiji University , Tama-ku, Kawasaki , Japan.
b Department of Nutrition , Kagawa Nutrition University , Sakado , Japan.
Biosci Biotechnol Biochem. 2018 Feb;82(2):312-319. doi: 10.1080/09168451.2017.1422971. Epub 2018 Jan 10.
Advanced glycation end products (AGEs) formed from glyceraldehyde (Gcer) and glycolaldehyde (Gcol) are involved in the pathogenesis of diabetic complications, via interactions with a receptor for AGEs (RAGE). In this study, we aimed to elucidate the RAGE-binding structure in Gcer and Gcol-derived AGEs and identify the minimal moiety recognized by RAGE. Among Gcer and Gcol-derived AGEs, GLAP (glyceraldehyde-derived pyridinium) and GA-pyridine elicited toxicity in PC12 neuronal cells. The toxic effects of GLAP and GA-pyridine were suppressed in the presence of anti-RAGE antibody or the soluble form of RAGE protein. Furthermore, the cytotoxicity test using GLAP analog compounds indicated that the 3-hydroxypyridinium (3-HP) structure is sufficient for RAGE-dependent toxicity. Surface plasmon resonance analysis showed that 3-HP derivatives directly interact with RAGE. These results indicate that GLAP and GA-pyridine are RAGE-binding epitopes, and that 3-HP, a common moiety of GLAP and GA-pyridine, is essential for the interaction with RAGE.
由甘油醛（Gcer）和乙醇醛（Gcol）形成的晚期糖基化终末产物（AGEs）通过与AGE受体（RAGE）相互作用，参与糖尿病并发症的发病机制。在本研究中，我们旨在阐明Gcer和Gcol衍生的AGEs中的RAGE结合结构，并确定RAGE识别的最小部分。在Gcer和Gcol衍生的AGEs中，GLAP（甘油醛衍生的吡啶鎓）和GA-吡啶在PC12神经元细胞中引发毒性。在抗RAGE抗体或RAGE蛋白的可溶性形式存在下，GLAP和GA-吡啶的毒性作用受到抑制。此外，使用GLAP类似物化合物的细胞毒性试验表明，3-羟基吡啶鎓（3-HP）结构足以产生RAGE依赖性毒性。表面等离子体共振分析表明，3-HP衍生物直接与RAGE相互作用。这些结果表明，GLAP和GA-吡啶是RAGE结合表位，并且3-HP作为GLAP和GA-吡啶的共同部分，对于与RAGE的相互作用至关重要。
