Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.
Age-dependent increase in ortho-tyrosine and methionine sulfoxide in human skin collagen is not accelerated in diabetes. Evidence against a generalized increase in oxidative stress in diabetes.
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DOI：
10.1172/jci119599
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发表时间：
1997-08
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影响因子：
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通讯作者：
M. Wells-Knecht;T. Lyons;D. McCance;S. Thorpe;J. Baynes
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文献类型：
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作者：
M. Wells-Knecht;T. Lyons;D. McCance;S. Thorpe;J. Baynes
糖氧化产物纳尔逊-（羧甲基）赖氨酸和戊苷在皮肤胶原蛋白中随着年龄的增长而增加，在糖尿病中以更快的速度增加。它们在皮肤胶原蛋白中的年龄调整浓度与糖尿病并发症的严重程度相关。为了确定糖基化和/或氧化在糖尿病患者糖氧化产物加速形成中的相对作用，我们测量了氨基酸氧化产物的水平，不同于氨基酸的糖氧化修饰，作为衰老和糖尿病中氧化应激和胶原损伤的独立指标。我们发现，在体外胶原糖氧化过程中，正酪氨酸和蛋氨酸亚砜会与纳尔逊-（羧甲基）赖氨酸和戊苷一起形成，并且它们也会随着年龄的增长而增加。在糖尿病和非糖尿病受试者中，胶原蛋白中这些氧化氨基酸的年龄调整水平是相同的，这表明糖尿病本身不会导致氧化应激增加或细胞外基质蛋白损伤。这些结果为胶原蛋白氧化损伤的年龄依赖性增加提供了证据，并支持了先前的结论，即糖尿病患者皮肤胶原蛋白中糖氧化产物的增加可以单独通过血糖升高来解释，而不是引起糖尿病依赖性氧化应激的普遍增加。
The glycoxidation products Nepsilon-(carboxymethyl)lysine and pentosidine increase in skin collagen with age and at an accelerated rate in diabetes. Their age-adjusted concentrations in skin collagen are correlated with the severity of diabetic complications. To determine the relative roles of increased glycation and/or oxidation in the accelerated formation of glycoxidation products in diabetes, we measured levels of amino acid oxidation products, distinct from glycoxidative modifications of amino acids, as independent indicators of oxidative stress and damage to collagen in aging and diabetes. We show that ortho-tyrosine and methionine sulfoxide are formed in concert with Nepsilon-(carboxymethyl)lysine and pentosidine during glycoxidation of collagen in vitro, and that they also increase with age in human skin collagen. The age-adjusted levels of these oxidized amino acids in collagen was the same in diabetic and nondiabetic subjects, arguing that diabetes per se does not cause an increase in oxidative stress or damage to extracellular matrix proteins. These results provide evidence for an age-dependent increase in oxidative damage to collagen and support previous conclusions that the increase in glycoxidation products in skin collagen in diabetes can be explained by the increase in glycemia alone, without invoking a generalized, diabetes-dependent increase in oxidative stress.