Significance of fructose-induced protein oxidation and formation of advanced glycation end product.
To investigate the significance of fructose-induced protein modification, we examined both fructose- and glucose-induced protein oxidation and the formation of advanced glycation end products (AGE) in vitro. Albumin incubated in the presence of 100 mM fructose at 37 degrees C for 1 week showed 5.1-fold and 3.1-fold increases in the content of carbonyl, which is a marker for oxidized protein, when compared with either control incubated without sugar or with 100 mM glucose. Similarly, the same incubation with fructose increased the fluorescence intensity over 100-fold and 15-fold formation compared with that of no sugar and glucose controls, respectively. Both fructose-induced fluorescence and protein oxidation were almost completely suppressed in the presence of the iron chelator; deferoxamine (100 microM), the hydroxyl radical scavenger; MK-447 (1 mM), or aminoguanidine (200 mM), which is an inhibitor of AGE formation. In contrast, the fructose-induced formation of fluorescent albumin was potentiated in the presence of 100 microM FeCl2. This was completely inhibited in the presence of 60 microM or more deferoxamine. These results suggest that fructose promotes both AGE formation and protein oxidation possibly through the formation of hydroxyl radicals.
Takagi
Y
Y
Third Department of Medicine, Shiga University of Medical Science, Japan.
Kashiwagi
A
A
Tanaka
Y
Y
Asahina
T
T
Kikkawa
R
R
Shigeta
Y
Y
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002084:Butylated Hydroxytoluene / Q000031:analogs & derivatives; D003676:Deferoxamine; D004140:Dinitrophenols; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D005632:Fructose; D017127:Glycation End Products, Advanced / Q000032:analysis*; D007700:Kinetics; D015999:Multivariate Analysis; D012710:Serum Albumin, Bovine; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004140:Dinitrophenols; D005296:Ferrous Compounds; D016166:Free Radical Scavengers; D017127:Glycation End Products, Advanced; C034638:dinitrophenyl-bovine serum albumin; D002084:Butylated Hydroxytoluene; D012710:Serum Albumin, Bovine; D005632:Fructose; C013753:2-aminomethyl-4-t-butyl-6-iodophenol; D003676:Deferoxamine; C029451:ferrous chloride