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- Title
Receptor for advanced glycation end products (RAGE)-mediated cytotoxicity of 3-hydroxypyridinium derivatives.
- Authors
Murakami, Yoto; Fujino, Takayuki; Hasegawa, Toshiki; Kurachi, Ryotaro; Miura, Aya; Daikoh, Takumi; Usui, Teruyuki; Hayase, Fumitaka; Watanabe, Hirohito
- Abstract
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.
- Subjects
ADVANCED glycation end-products; NEUROTOXICOLOGY
- Publication
Bioscience, Biotechnology & Biochemistry, 2018, Vol 82, Issue 2, p312
- ISSN
0916-8451
- Publication type
Article
- DOI
10.1080/09168451.2017.1422971