Identification in human atherosclerotic lesions of GA-pyridine, a novel structure derived from glycolaldehyde-modified proteins.
Glycolaldehyde (GA) is formed from serine by action of myeloperoxidase and reacts with proteins to form several products. Prominent among them is N(epsilon)-(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(alpha)-(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.
Nagai
Ryoji
R
Department of Biochemistry and Second Department of Pathology, Kumamoto University School of Medicine, Japan.
Hayashi
Cristina Miki
CM
Xia
Ling
L
Takeya
Motohiro
M
Horiuchi
Seikoh
S
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000737:chemistry*; D000368:Aged; D000369:Aged, 80 and over; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D002851:Chromatography, High Pressure Liquid; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011506:Proteins / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry / Q000378:metabolism*
D011506:Proteins; D011725:Pyridines; D000079:Acetaldehyde; C023666:pyridine; C010972:glycolaldehyde