Identification in Human Atherosclerotic Lesions of GA-pyridine, a Novel Structure Derived from Glycolaldehyde-modified Proteins

• Published in: The Journal of biological chemistry 2002-12, Vol.277 (50), p.48905-48912
• Main Authors: Nagai, Ryoji, Hayashi, Cristina Miki, Xia, Ling, Takeya, Motohiro, Horiuchi, Seikoh
• Format: Article
• Language: English
• Subjects: Acetaldehyde - analogs & derivatives; Acetaldehyde - chemistry; Aged; Aged, 80 and over; Arteriosclerosis - metabolism; Arteriosclerosis - pathology; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunohistochemistry; Male; Proteins - chemistry; Pyridines - chemistry; Pyridines - metabolism
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M205688200

Glycolaldehyde (GA) is formed from serine by action of myeloperoxidase and reacts with proteins to form several products. Prominent among them is N ε -(carboxymethyl)lysine (CML), which is also known as one of the advanced glycation end products. Because CML is formed from a wide range of precursors, we have attempted to identify unique structures characteristic of the reaction of GA with protein. To this end, monoclonal (GA5 and 1A12) and polyclonal (non-CML-GA) antibodies specific for GA-modified proteins were prepared. These antibodies specifically reacted with GA-modified and with hypochlorous acid-modified BSA, but not with BSA modified by other aldehydes, indicating that the epitope of these antibodies could be a specific marker for myeloperoxidase-induced protein modification. By HPLC purification from GA-modified N α -(carbobenzyloxy)- l -lysine, GA5-reactive compound was isolated, and its chemical structure was characterized as 3-hydroxy-4-hydroxymethyl-1-(5-amino-5-carboxypentyl) pyridinium cation. This compound named as GA-pyridine was recognized both by 1A12 and non-CML-GA, indicating that GA-pyridine is an important antigenic structure in GA-modified proteins. Immunohistochemical studies with GA5 demonstrated the accumulation of GA-pyridine in the cytoplasm of foam cells and extracellularly in the central region of atheroma in human atherosclerotic lesions. These results suggest that myeloperoxidase-mediated protein modification via GA may contribute to atherogenesis.