Nonenzymatic glycation of transferrin: decrease of iron-binding capacity and increase of oxygen radical production.
The total iron-binding capacity (TIBC) and iron contents of diabetic rat serum, as well as the iron-binding capacity of glycated transferrin and oxygen radical production by the glycated proteins were examined. The TIBC and iron content of diabetic rat sera were found to be much lower than those of control rat sera. Incubation of human serum with glucose in vitro resulted in a significant fall of its unsaturated iron-binding capacity (UIBC) with time. When apotransferrin was incubated with glucose, its UIBC significantly decreased. The iron content of holotransferrin was markedly reduced by incubation with bathophenanthroline sulphonic acid (BPSA) in the presence of glucose, although the content was not altered by incubation with BPSA alone. The generation of superoxide radical (O2-) and hydroxyl radical (OH.) by the glycated holotransferrin was much greater than that by glycated apotransferrin. Glycated holotransferrin showed significantly accelerated hydroxyl radical production by the hypoxanthine-xanthine oxidase system, while intact holotransferrin did not. Treatment of holotransferrin with glucose caused the fragmentation of the protein, while the same treatment of apotransferrin did not. These results suggest that iron ions in the glycated transferrin molecule are bound loosely to the protein and are redox-active and the glycated holotransferrin produces oxygen radicals including O2- and OH. efficiently, and that the glycated transferrin does not function as an iron-binding protein.
Fujimoto
S
S
Laboratory of Biochemistry, Kyoto Pharmaceutical University, Japan.
Kawakami
N
N
Ohara
A
A
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000097:blood*; D005609:Free Radicals / Q000097:blood; D005947:Glucose / Q000494:pharmacology; D006031:Glycosylation; D017665:Hydroxyl Radical / Q000097:blood*; D007501:Iron / Q000097:blood*; D008297:Male; D010100:Oxygen / Q000097:blood*; D051381:Rats; D017208:Rats, Wistar; D013481:Superoxides / Q000097:blood*; D014168:Transferrin / Q000378:metabolism*
D005609:Free Radicals; D014168:Transferrin; D013481:Superoxides; D017665:Hydroxyl Radical; D007501:Iron; D005947:Glucose; D010100:Oxygen