Macrophage Recognition of Toxic Advanced Glycosylation End Products through the Macrophage Surface-Receptor Nucleolin
| Autor: | Mio Konishi, Kazuya Hirano, Yoshihiro Tachibana, Hikaru Dambara, Yuichi Miki, Masatoshi Beppu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Glycation End Products
Advanced Male Glycosylation Arginine Serum albumin Pharmaceutical Science Acetaldehyde Biology Glyceraldehyde Transfection Mice chemistry.chemical_compound Animals Humans Macrophage skin and connective tissue diseases Cytotoxicity Receptor Pharmacology Macrophages RNA-Binding Proteins Serum Albumin Bovine General Medicine Aptamers Nucleotide Phosphoproteins Molecular biology HEK293 Cells Oligodeoxyribonucleotides Biochemistry chemistry Immunoglobulin G biology.protein Cattle Antibody Nucleolin |
| Zdroj: | Biological and Pharmaceutical Bulletin. 37:588-596 |
| ISSN: | 1347-5215 0918-6158 |
| Popis: | Advanced glycosylation end-products (AGEs) are non-enzymatically glycosylated proteins that play an important role in several diseases and aging processes, including angiopathy, renal failure, diabetic complications, and some neurodegenerative diseases. In particular, glyceraldehyde (GCA)- and glycolaldehyde (GOA)-derived AGEs are deemed toxic AGEs, due to their cytotoxicity. Recently, the shuttling-protein nucleolin has been shown to possess scavenger receptor-activity. Here, we investigated whether or not macrophages recognize toxic AGEs through nucleolin receptors expressed on their surface. Free amino acid groups and arginine residues found in bovine serum albumin (BSA) were time-dependently modified by incubation with GCA and GOA. In addition, average molecular size was increased by incubation with GCA and GOA. While GCA-treated BSA (GCA-BSA) and GOA-treated BSA (GOA-BSA) were recognized by thioglycollate-elicited mouse peritoneal macrophages in proportion to their respective aldehyde-modification ratios, aldehyde-untreated control-BSA was not. Surface plasmon-resonance analysis revealed that nucleolin strongly associated with GCA-BSA and GOA-BSA, but not with control-BSA. Further, pretreating macrophages with anti-nucleolin antibody, but not control-Immunoglobulin G, inhibited recognition of GCA-BSA and GOA-BSA by macrophages. Additionally, AGRO, a nucleolin-specific oligonucleotide aptamer, inhibited recognition of GCA-BSA and GOA-BSA. Moreover, nucleolin-transfected HEK293 cells recognized more GCA-BSA and GOA-BSA than control HEK cells did. Binding of nucleolin and GCA-BSA/GOA-BSA was also blocked by anti-nucleolin antibody at molecular level. These results indicate that nucleolin is a receptor that allows macrophages to recognize toxic AGEs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|