%0 Journal Article %A Murakami, Yoto %A Fujino, Takayuki %A Hasegawa, Toshiki %A Kurachi, Ryotaro %A Miura, Aya %A Daikoh, Takumi %A Usui, Teruyuki %A Hayase, Fumitaka %A Watanabe, Hirohito %D 2018 %T Receptor for advanced glycation end products (RAGE)-mediated cytotoxicity of 3-hydroxypyridinium derivatives %U https://tandf.figshare.com/articles/journal_contribution/Receptor_for_advanced_glycation_end_products_RAGE_-mediated_cytotoxicity_of_3-hydroxypyridinium_derivatives/5772978 %R 10.6084/m9.figshare.5772978.v1 %2 https://tandf.figshare.com/ndownloader/files/10181976 %K Advanced glycation end products %K glyceraldehyde %K glycolaldehyde %K receptor for advanced glycation end products %K 3-Hydroxypyridinium %K AGEs: advanced glycation end products %K Gcer: glyceraldehyde %K Gcol: glycolaldehyde %K RAGE: receptor for advanced glycation end products %K 3-HP: 3-hydroxypyridinium %K NAC: N-acetylcysteine %K ROS: reactive oxygen species %K DAPI: 6-diamidino-2-phenylindole %K GST: glutathione S-transferase %K SPR: surface plasmon resonance %X

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.

GLAP and GA-pyridine are RAGE-binding AGEs, and the 3-hydroxypyridinium moiety is sufficient for the interaction with RAGE.

%I Taylor & Francis