Increased accumulation of the glycoxidation product N-epsilon(carboxymethyl)lysine in human tissues in diabetes and aging
Increased accumulation of the glycoxidation product N-epsilon(carboxymethyl)lysine in human tissues in diabetes and aging
复制标题
DOI：
10.1172/jci119180
复制
发表时间：
1997-02-01
影响因子：
15.9
通讯作者：
Nerlich, AG
中科院分区：
文献类型：
--
作者：
Schleicher, ED;Wagner, E;Nerlich, AG
N-羧甲基赖氨酸（CML）是糖化蛋白氧化修饰的主要产物，已被认为是衰老、动脉粥样硬化和糖尿病中氧化应激和蛋白质长期损伤的一般标志物。为了研究CML在人类中的发生和分布，产生了特异性识别蛋白结合CML的抗血清。从糖化蛋白的CML的氧化形成减少了由硫辛酸，氨基胍，超氧化物歧化酶，过氧化氢酶，特别是维生素E和去铁胺。CML在皮肤、肺、心脏、肾、肠、椎间盘，特别是动脉中的免疫定位提供了CML在不同部位积累的年龄依赖性增加以及糖尿病中该过程加速的证据。动脉壁，特别是弹性膜染色强烈，动脉粥样硬化斑块和泡沫细胞内CML修饰程度高。慢性粒细胞白血病的免疫反应性病变的优先位置可能表明糖基化的糖尿病和衰老过程中发生的贡献。此外，我们发现糖尿病患者血清蛋白中CML含量增加。CML形成对氧化条件的强烈依赖性以及糖尿病血清和组织蛋白中CML发生率的增加表明CML作为氧化损伤的内源性生物标志物的作用。
N-epsilon-(Carboxymethyl)lysine (CML), a major product of oxidative modification of glycated proteins, has been suggested to represent a general marker of oxidative stress and longterm damage to proteins in aging, atherosclerosis, and diabetes. To investigate the occurrence and distribution of CML in humans an antiserum specifically recognizing protein-bound CML was generated. The oxidative formation of CML from glycated proteins was reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, and particularly vitamin E and desferrioxamine. Immunolocalization of CML in skin, lung, heart, kidney, intestine, intervertebral discs, and particularly in arteries provided evidence for an age-dependent increase in CML accumulation in distinct locations, and acceleration of this process in diabetes. Intense staining of the arterial wall and particularly the elastic membrane was found. High levels of CML modification were observed within atherosclerotic plaques and in foam cells. The preferential location of CML immunoreactivity in lesions may indicate the contribution of glycoxidation to the processes occurring in diabetes and aging. Additionally, we found increased CML content in serum proteins in diabetic patients. The strong dependence of CML formation on oxidative conditions together with the increased occurrence of CML in diabetic serum and tissue proteins suggest a role for CML as endogenous biomarker for oxidative damage.