title: Oxidative modification of ferritin induced by methylglyoxal.
abstract: Methylglyoxal (MG) was identified as an intermediate in non-enzymatic glycation and increased levels were reported in patients with diabetes. In this study, we evaluated the effects of MG on the modification of ferritin. When ferritin was incubated with MG, covalent crosslinking of the protein increased in a time- and MG dose-dependent manner. Reactive oxygen species (ROS) scavengers, N-acetyl-(L)-cysteine and thiourea suppressed the MG-mediated ferritin modification. The formation of dityrosine was observed in MG-mediated ferritin aggregates and ROS scavengers inhibited the formation of dityrosine. During the reaction between ferritin and MG, the generation of ROS was increased as a function of incubation time. These results suggest that ROS may play a role in the modification of ferritin by MG. The reaction between ferritin and MG led to the release of iron ions from the protein. Ferritin exposure to MG resulted in a loss of arginine, histidine and lysine residues. It was assumed that oxidative damage to ferritin caused by MG may induce an increase in the iron content in cells, which is deleterious to cells. This mechanism, in part, may provide an explanation or the deterioration of organs under diabetic conditions.
authors.affiliation: Department of Genetic Engineering, Cheongju University, Cheongju, Korea.
authors.forename: Sung Ho
authors.initials: SH
authors.lastname: An
authors.forename: Myeong Seon
authors.initials: MS
authors.lastname: Lee
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
mesh_terms: D004305:Dose-Response Relationship, Drug; D005293:Ferritins / Q000378:metabolism*; D016166:Free Radical Scavengers / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D011765:Pyruvaldehyde / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D014443:Tyrosine; D011765:Pyruvaldehyde; D005293:Ferritins; C007543:dityrosine