Modification and inactivation of human Cu,Zn-superoxide dismutase by methylglyoxal.
Methylglyoxal (MG) has been identified as an intermediate in non-enzymatic glycation, and increased levels have been reported in patients with diabetes. In this study, the effect of MG on the structure and function of human Cu,Zn-superoxide dismutase (SOD) was investigated. MG modifies Cu,Zn-SOD, as indicated by the formation of fluorescent products. When Cu, Zn-SOD was incubated with MG, covalent crosslinking of the protein increased progressively. MG-mediated modification of Cu,Zn-SOD led to loss of enzymatic activity and release of copper ions from the protein. Radical scavengers inhibited the crosslinking of Cu,Zn-SOD. When Cu,Zn-SOD that had been exposed to MG was analyzed, glycine, histidine, lysine, and valine residues were found to be particularly sensitive. It is suggested that oxidative damage to Cu,Zn-SOD by MG may perturb cellular antioxidant defense systems and damage cells. This effect may account, in part, for organ deterioration in diabetes.
Kang
Jung Hoon
JH
Department of Genetic Engineering, Chongju University, Chongju 360-764, Korea. jhkang@chongju.ac.kr
D003432:Cross-Linking Reagents / Q000378:metabolism; D006801:Humans; D011765:Pyruvaldehyde / Q000378:metabolism*; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000737:chemistry / Q000378:metabolism*
D003432:Cross-Linking Reagents; D011765:Pyruvaldehyde; D013482:Superoxide Dismutase