Oxidative damage of DNA by the reaction of amino acid with methylglyoxal in the presence of Fe(III).
Methylglyoxal (MG) is an endogenous metabolite which is present in increased concentrations in diabetics and reacts with amino acids to form advanced glycation end products. DNA cleavage induced by the reaction of MG with lysine in the presence of Fe3+ was investigated. When plasmid DNA was incubated with MG and lysine in the presence of Fe3+, DNA strand breakage was proportional to MG and lysine concentrations. The formation of superoxide anion was detected during this reaction, and catalase, hydroxyl radical scavengers and iron chelator, desferrioxamine inhibited DNA cleavage. Deoxyribose assays showed that hydroxyl radicals were generated during the MG/lysine/Fe3+ reaction. These results suggest that superoxide anion and H2O2 may be generated from the glycation reaction between lysine with MG, and that Fe3+ probably participates in a Fenton's type reaction to produce hydroxyl radicals, which may cause DNA cleavage. This mechanism, in part, may provide an explanation for the deterioration of organs under diabetic conditions.
Kang
Jung Hoon
JH
Department of Genetic Engineering, Chongju University, Chongju 360-764, South Korea. jhkang@chongju.ac.kr
D002374:Catalase / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D003676:Deferoxamine / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry; D017665:Hydroxyl Radical / Q000737:chemistry; D007501:Iron / Q000737:chemistry* / Q000378:metabolism; D007502:Iron Chelating Agents / Q000737:chemistry; D008239:Lysine / Q000737:chemistry / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011765:Pyruvaldehyde / Q000737:chemistry* / Q000378:metabolism; D013481:Superoxides / Q000737:chemistry / Q000378:metabolism
D016166:Free Radical Scavengers; D007502:Iron Chelating Agents; D013481:Superoxides; D017665:Hydroxyl Radical; D011765:Pyruvaldehyde; D007501:Iron; D002374:Catalase; D003676:Deferoxamine; D008239:Lysine