Takayama F, Aoyama I, Tsukushi S, Miyazaki T, Miyazaki S, Morita T, Hirasawa Y, Shimokata K, Niwa T
Nagoya University Daiko Medical Center, Japan.
Cell Mol Biol (Noisy-le-grand). 1998 Nov;44(7):1101-9.
The modification of long-lived proteins with advanced glycation endproducts (AGEs) has been hypothesised to contribute to the development of pathologies associated with uremia. Imidazolone and N(epsilon)-(carboxymethyl)lysine (CML) are common epitopes of AGE-modified proteins. Imidazolone is a reaction product of arginine with 3-deoxyglucosone (3-DG) which is markedly accumulated in uremic serum. CML is produced by glycoxidation, and represents a marker of oxidative stress. The specificity of anti-imidazolone antibody that we had developed was further examined using ELISA. The antibody reacted only with imidazolone derived from 3-DG and arginine, but did not react at all with the other imidazolone-like compounds such as reaction products of glyoxal, methylglyoxal, glucosone with arginine or a reaction product of 3-DG with creatine. Further, to determine if AGEs are involved in the development of atherosclerosis in hemodialysis (HD) patients, we studied the localisation of imidazolone and CML in the aortas obtained from HD patients by immunohistochemistry using the anti-imidazolone and anti-CML antibodies. Imidazolone and CML were localised in all atherosclerotic aortic walls of the HD patients. In conclusion, imidazolone and CML are localised in the characteristic lesions of atherosclerosis in HD patients. These results strongly suggest that imidazolone produced by 3-DG, and CML produced by glycoxidation may contribute to the development of atherosclerosis in uremic patients.
晚期糖基化终产物（AGEs）对长寿蛋白的修饰被认为与尿毒症相关病理状况的发展有关。咪唑啉酮和N-ε-（羧甲基）赖氨酸（CML）是AGE修饰蛋白的常见表位。咪唑啉酮是精氨酸与3-脱氧葡萄糖酮（3-DG）的反应产物，3-DG在尿毒症血清中显著蓄积。CML由糖氧化产生，是氧化应激的标志物。我们使用酶联免疫吸附测定（ELISA）进一步检测了所研发的抗咪唑啉酮抗体的特异性。该抗体仅与源自3-DG和精氨酸的咪唑啉酮反应，而与其他咪唑啉酮样化合物完全不反应，如乙二醛、甲基乙二醛、葡萄糖酮与精氨酸的反应产物或3-DG与肌酸的反应产物。此外，为确定AGEs是否参与血液透析（HD）患者动脉粥样硬化的发展，我们使用抗咪唑啉酮和抗CML抗体，通过免疫组织化学研究了HD患者主动脉中咪唑啉酮和CML的定位。咪唑啉酮和CML定位于HD患者所有动脉粥样硬化的主动脉壁中。总之，咪唑啉酮和CML定位于HD患者动脉粥样硬化的特征性病变中。这些结果强烈表明，由3-DG产生的咪唑啉酮和由糖氧化产生的CML可能参与了尿毒症患者动脉粥样硬化的发展。
