Kang Jung Hoon
Department of Genetic Engineering, Chongju University, Chongju 360-764, Korea.
Mol Cells. 2003 Apr 30;15(2):194-9.
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.
甲基乙二醛（MG）已被确定为非酶糖基化过程中的一种中间体，据报道糖尿病患者体内其水平会升高。在本研究中，研究了MG对人铜锌超氧化物歧化酶（SOD）结构和功能的影响。MG会修饰铜锌超氧化物歧化酶，这可通过荧光产物的形成来表明。当铜锌超氧化物歧化酶与MG一起孵育时，蛋白质的共价交联会逐渐增加。MG介导的铜锌超氧化物歧化酶修饰导致酶活性丧失以及铜离子从蛋白质中释放。自由基清除剂可抑制铜锌超氧化物歧化酶的交联。当分析暴露于MG的铜锌超氧化物歧化酶时，发现甘氨酸、组氨酸、赖氨酸和缬氨酸残基特别敏感。有人认为，MG对铜锌超氧化物歧化酶的氧化损伤可能会扰乱细胞抗氧化防御系统并损害细胞。这种作用可能部分解释了糖尿病中器官的恶化。
