Receptor for advanced glycation end products (RAGE)-mediated cytotoxicity of 3-hydroxypyridinium derivatives
| Autor: | Teruyuki Usui, Hirohito Watanabe, Takayuki Fujino, Toshiki Hasegawa, Ryotaro Kurachi, Aya Miura, Fumitaka Hayase, Yoto Murakami, Takumi Daikoh |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
endocrine system diseases Pyridines Receptor for Advanced Glycation End Products Acetaldehyde medicine.disease_cause Glyceraldehyde Applied Microbiology and Biotechnology Biochemistry PC12 Cells Epitope Analytical Chemistry RAGE (receptor) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glycation medicine Animals Humans cardiovascular diseases Cytotoxicity Receptor Molecular Biology biology Chemistry Cytotoxins Organic Chemistry nutritional and metabolic diseases General Medicine Rats Oxidative Stress 030104 developmental biology biology.protein cardiovascular system Antibody human activities 030217 neurology & neurosurgery Oxidative stress Biotechnology |
| Zdroj: | Bioscience, biotechnology, and biochemistry. 82(2) |
| ISSN: | 1347-6947 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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