Imidazolone, a novel advanced glycation end product, is present at high levels in kidneys of rats with streptozotocin-induced diabetes.
We produced a monoclonal antibody to imidazolones A and B, novel advanced glycation end products formed from the reaction of 3-deoxyglucosone (3-DG) with the guanidino group of arginine. Liquid chromatography/mass spectrometry demonstrated that the formation of imidazolone A by incubating 3-DG with arginine is very rapid, reaching a maximum concentration within 24 h, but the formation of imidazolone B is very slow and low in quantity even after 2 weeks. Thus, at physiological conditions the formation of imidazolone A is dominant, while that of imidazolone B is negligible. Immunochemistry demonstrated that the imidazolone content in the kidneys of streptozotocin-induced diabetic rats was significantly higher than in the control rats. Serum levels of 3-DG in the diabetic rats were also significantly higher than in control rats. 3-DG attacks the arginine residues of the tissue proteins, producing imidazolone at high levels in the kidneys affected by diabetic nephropathy.
Niwa
T
T
Nagoya University Daiko Medical Center, Higashi-ku, Japan.
Katsuzaki
T
T
Ishizaki
Y
Y
Hayase
F
F
Miyazaki
T
T
Uematsu
T
T
Tatemichi
N
N
Takei
Y
Y
D000818:Animals; D000911:Antibodies, Monoclonal; D001120:Arginine / Q000031:analogs & derivatives* / Q000276:immunology / Q000378:metabolism; D003847:Deoxyglucose / Q000031:analogs & derivatives / Q000097:blood; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003928:Diabetic Nephropathies / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000276:immunology / Q000378:metabolism*; D007093:Imidazoles / Q000276:immunology / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D015416:Maillard Reaction; D008297:Male; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
C105210:2-benzamido-5-(5-((2,3,4-trihydroxybutyl)-4-oxo-2-imidazolin-2-yl)amino)pentanamide; C105229:2-benzamido-5--(5-((2,3,4-trihydroxybutyl)-4-oxoimidazol-2-yl)amino)pentanamide; D000911:Antibodies, Monoclonal; D017127:Glycation End Products, Advanced; D007093:Imidazoles; D001120:Arginine; D003847:Deoxyglucose; C016350:3-deoxyglucosone