Advanced oxidation protein products as a novel marker of oxidative stress in uremia
Advanced oxidation protein products as a novel marker of oxidative stress in uremia
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DOI：
10.1038/ki.1996.186
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发表时间：
1996-05-01
影响因子：
19.6
通讯作者：
DescampsLatscha, B
中科院分区：
文献类型：
--
作者：
WitkoSarsat, V;Friedlander, M;DescampsLatscha, B
有证据表明，抗氧化剂和氧化剂生成系统之间的失衡导致尿毒症患者的氧化应激。由于血浆蛋白是氧化剂的关键靶点，我们开发了一种新的分光光度法，可以检测尿毒症血浆中的晚期氧化蛋白产物（AOPP）。通过分子排阻层析，在尿毒症血浆中检索到AOPP在600和低于50 kDa的两个不同峰，而在对照血浆中没有发现这样的峰。进一步的生化表征显示AOPP由氧化的血浆蛋白，尤其是白蛋白携带，并且不具有氧化性质。血浆或纯化人血清白蛋白（HSA）体外暴露于次氯酸后，AOPP以剂量依赖性方式增加。晚期糖基化终产物人血清白蛋白（AGE-HSA）也增加AOPP水平。在体内，血液透析患者的AOPP血浆水平最高，其次是腹膜透析患者和未透析的晚期慢性肾功能衰竭患者。AOPP水平与血浆二酪氨酸和AGE-戊糖苷浓度相关，作为氧化剂介导的蛋白质损伤的指标，但与硫代巴比妥反应物质作为脂质过氧化标记物无关。AOPP和新喋呤水平之间也存在密切的相关性，表明AOPP可能是尿毒症相关的单核细胞介导的炎症性疾病的一部分。总之，我们建议AOPP的测量作为一个可靠的标志物，以估计尿毒症患者氧化剂介导的蛋白质损伤的程度，并预测旨在减少这种氧化应激的治疗策略的潜在疗效。
Evidence suggests an imbalance between antioxidant and oxidant-generating systems resulting in oxidative stress in uremic patients. As plasma proteins are critical targets for oxidants, we developed a novel spectrophotometric assay which allows to detect advanced oxidation protein products (AOPP) in uremic plasma. By size-exclusion chromat raphy AOPP are retrieved in two distinct peaks at 600 and below SO kDa in uremic plasma, while no such peaks are found in control plasma. Further biochemical characterization revealed that AOPP are carried by oxidized plasma proteins, especially albumin and do not have oxidant properties. AOPP increased in a dose-dependent manner following in vitro exposure of plasma or purified human serum albumin (HSA) to hypochlorous acid. Advanced glycation end products of human serum albumin (AGE-HSA) also increased AOPP levels. In vivo, plasma level of AOPP was the highest in patients on hemodialysis, followed by those on peritoneal dialysis and by undialyzed patients with advanced chronic renal failure. AOPP levels correlated with plasma concentrations of dityrosine and AGE-pentosidine, as indices of oxidant-mediated protein damage, but not with thiobarbituric reactive substances as lipid peroxidation markers. A close correlation was also found between AOPP and neopterin levels, suggesting that AOPP could be part in the monocyte-mediated inflammatory disorders associated with uremia. In conclusion, we propose the measurement of AOPP as a reliable marker to estimate the degree of oxidant-mediated protein damage in uremic patients and to predict the potential efficacy of therapeutic strategies aimed at reducing such an oxidative stress.