Structure-function analysis of the antioxidant properties of haptoglobin
Structure-function analysis of the antioxidant properties of haptoglobin
复制标题
DOI：
10.1182/blood.v98.13.3693
复制
发表时间：
2001-12-15
期刊：
影响因子：
20.3
通讯作者：
Levy, AP
中科院分区：
文献类型：
--
作者：
Melamed-Frank, M;Lache, O;Levy, AP
触珠蛋白是一种抗氧化剂，它具有防止血红蛋白引起的氧化性组织损伤的能力。最近有研究表明，触珠蛋白基因的等位基因多态性可预测多种微血管和大血管糖尿病并发症的风险。由于这些并发症在很大程度上归因于氧化应激的增加，因此进行了一项研究，以确定2种触珠蛋白等位基因的不同蛋白质产物在提供的抗氧化保护方面是否存在差异。两种不同等位基因产生的纯化触珠蛋白的抗氧化能力存在统计学上的显著差异，这与基因决定的抗氧化状态的差异可能解释糖尿病血管并发症易感性的假设相一致。这些差异可能在血管壁中被放大，因为接触珠蛋白类型的筛分能力不同。因此，我们试图鉴定出体外抑制血红蛋白氧化所需的最小接触珠蛋白序列，并鉴定出2个独立的接触珠蛋白肽，它们在这种方式下与天然接触珠蛋白一样有效。确定不同类型的触珠蛋白差异的生化基础可能会导致新的药物的合理开发，如这里描述的微型触珠蛋白，以避免糖尿病血管并发症的发展。(C) 2001年由美国血液学会出版。
Haptoglobin serves as an antioxidant by virtue of its ability to prevent hemoglobin-driven oxidative tissue damage. It was recently demonstrated that an allelic polymorphism in the haptoglobin gene is predictive of the risk for numerous microvascular and macrovascular diabetic complications. Because these complications are attributed in large part to an increase in oxidative stress, a study was conducted to determine whether the different protein products of the 2 haptoglobin alleles differed in the antioxidant protection they provided. A statistically significant difference was found in the antioxidant capacity of purified haptoglobin protein produced from the 2 different alleles, consistent with the hypothesis that differences in genetically determined antioxidant status may explain differential susceptibility to diabetic vascular complications. These differences may be amplified in the vessel wall because of differences in the sieving capacity of the haptoglobin types. Therefore, an attempt was made to identify the minimal haptoglobin sequences necessary to inhibit oxidation by hemoglobin in vitro, and 2 independent haptoglobin peptides that function in this fashion as efficiently as native haptoglobin were identified. Identification of the biochemical basis for differences among haptoglobin types may lead to the rational development of new pharmacologic agents, such as the mini-haptoglobin described here, to avert the development of diabetic vascular complications. (C) 2001 by The American Society of Hematology.