OXIDATION OF GLYCATED PROTEINS - AGE-DEPENDENT ACCUMULATION OF N-EPSILON-(CARBOXYMETHYL)LYSINE IN LENS PROTEINS
OXIDATION OF GLYCATED PROTEINS - AGE-DEPENDENT ACCUMULATION OF N-EPSILON-(CARBOXYMETHYL)LYSINE IN LENS PROTEINS
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DOI：
10.1021/bi00450a033
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发表时间：
1989-11-28
期刊：
影响因子：
2.9
通讯作者：
BAYNES, JW
中科院分区：
文献类型：
--
作者：
DUNN, JA;PATRICK, JS;BAYNES, JW
N ε-（羧甲基）赖氨酸（CML）已被鉴定为体外糖化（非酶促糖基化）蛋白中果糖赖氨酸（FL）氧化的产物，并且也已在人体组织和尿中检测到[Ahmed等（1986）J.Biol.Chem.261，4889-4894]。在这项研究中，我们比较了正常人透镜蛋白，年龄为0.79岁，使用特定的和敏感的检测选择离子监测气相色谱-质谱法的基础上的CML和FL的量。我们的研究结果表明，FL的透镜含量在婴儿期和大约5岁之间显著增加，但在5岁和80岁之间FL只有轻微的、统计学上不显著的增加（平均值± 0.001）。标准差= 1.4 ±。0.4 mmol FL/mol Lys）。与此相反，透镜的氧化产物，CML，含量随年龄线性增加，范围从微量水平在婴儿期到8毫摩尔CML/摩尔赖氨酸在79岁。CML与FL的比率在1岁至79岁之间也分别从0.5摩尔CML/摩尔FL线性增加至5摩尔CML/摩尔FL。这些结果表明，CML，而不是FL，是在成人透镜蛋白中可检测到的糖基化的主要产物。CML在透镜蛋白中的年龄依赖性积累表明，随着年龄的增长，糖化和氧化产物在透镜中积累，而随着年龄的增长，CML在透镜中积累的恒定速率反对该组织中自由基防御机制的年龄依赖性下降。
N.epsilon.-(Carboxymethyl)lysine (CML) has been identified as a product of oxidation of fructoselysine (FL) in glycated (nonenzymatically glycosylated) proteins in vitro and has also been detected in human tissues and urine [Ahmed et al. (1986) J. Biol. Chem. 261, 4889-4894]. In this study, we compare the amounts of CML and FL in normal human lens proteins, aged 0.79 years, using specific and sensitive assays based on selected ion monitoring gas chromatography-mass spectrometry. Our results indicate that the lens content of FL increases significantly between infancy and about age 5 but that there is only a slight, statistically insignificant increase in FL between age 5 and 80 (mean .+-. SD = 1.4 .+-. 0.4 mmol of FL/mol of Lys). In contrast, the lens content of the oxidation product, CML, increased linearly with age, ranging from trace levels at infancy up to 8 mmol of CML/mol of lysine at age 79. The ratio of CML to FL also increased linearly from 0.5 to 5 mol of CML/mol of FL between age 1 and 79, respectively. These results indicate that CML, rather than FL, is the major product of glycation detectable in adult human lens protein. The age-dependent accumulation of CML in lens proteins indicates that products of both glycation and oxidation accumulate in the lens with age, while the constant rate of accumulation of CML in lens with age argues against an age-dependent decline in free radical defense mechanisms in this tissue.