Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes
Plasma protein advanced glycation end products, carboxymethyl cysteine, and carboxyethyl cysteine, are elevated and related to nephropathy in patients with diabetes
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DOI：
10.1007/s11010-007-9422-9
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发表时间：
2007-08-01
影响因子：
4.3
通讯作者：
El Said, Hala
中科院分区：
文献类型：
--
作者：
Mostafa, Ahmed A.;Randell, Edward W.;El Said, Hala
在糖尿病 (DM) 中，葡萄糖以及乙二醛和甲基乙二醛修饰蛋白质赖氨酸和精氨酸的游离氨基，形成晚期糖基化终产物 (AGE)。这些 AGE 水平升高与包括肾病在内的糖尿病并发症有关。我们的目的是测量糖尿病患者血浆蛋白中的羧甲基半胱氨酸 (CMC) 和羧乙基半胱氨酸 (CEC)，即通过这些醛修饰蛋白质的游离半胱氨酸巯基而形成的 AGE，并研究它们与肾病指标白蛋白肌酐比值（ACR，尿白蛋白 (mg)/肌酐 (mmol)）的关系。血液采集自 42 名 1 型和 2 型糖尿病患者（18-36 岁）和 18 名非糖尿病患者（17-35 岁）。开发了一种液相色谱-质谱联用方法来测量血浆蛋白 CMC 和 CEC 水平。获得了 ACR 和糖化血红蛋白 (HbA1C) 的值。与对照组（分别为 24.25 +/- 10.26、262.85 +/- 132.02）相比，DM 患者的平均血浆 CMC（μ g/l）和 CEC（μ g/l）显着较高（分别为 55.73 +/- 29.43、521.47 +/- 239.13）。在糖尿病患者中，CMC 和 CEC 与 ACR 呈正相关，HbA1C 也是如此。此外，CMC 或 CEC 与 HbA1C 相结合比单独使用这些变量中的任何一种更能预测肾病。这些结果表明葡萄糖、乙二醛和甲基乙二醛可能都与糖尿病肾病的病因有关。
In Diabetes Mellitus (DM), glucose and the aldehydes glyoxal and methylglyoxal modify free amino groups of lysine and arginine of proteins forming advanced glycation end products (AGEs). Elevated levels of these AGEs are implicated in diabetic complications including nephropathy. Our objective was to measure carboxymethyl cysteine (CMC) and carboxyethyl cysteine (CEC), AGEs formed by modification of free cysteine sulfhydryl groups of proteins by these aldehydes, in plasma proteins of patients with diabetes, and investigate their association with the albumin creatinine ratio (ACR, urine albumin (mg)/creatinine (mmol)), an indicator of nephropathy. Blood was collected from forty-two patients with type 1 and 2 diabetes (18-36 years) and eighteen individuals without diabetes (17-35 years). A liquid chromatography-mass spectrophotometric method was developed to measure plasma protein CMC and CEC levels. Values for ACR and hemoglobin A1C (HbA1C) were obtained. Mean plasma CMC (mu g/l) and CEC (mu g/l) were significantly higher in DM (55.73 +/- 29.43, 521.47 +/- 239.13, respectively) compared to controls (24.25 +/- 10.26, 262.85 +/- 132.02, respectively). In patients with diabetes CMC and CEC were positively correlated with ACR, as was HbA1C. Further, CMC or CEC in combination with HbA1C were better predictors of nephropathy than any one of these variables alone. These results suggest that glucose, glyoxal, and methylglyoxal may all be involved in the etiology of diabetic nephropathy.