An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species
An analog of the human albumin N-terminus (Asp-Ala-His-Lys) prevents formation of copper-induced reactive oxygen species
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DOI：
10.1006/bbrc.2001.5042
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发表时间：
2001-06-15
影响因子：
3.1
通讯作者：
Curtis, CG
中科院分区：
文献类型：
--
作者：
Bar-Or, D;Rael, LT;Curtis, CG
铜的动员和氧化还原活性形成破坏性的活性氧(ROS)，并与缺血再灌注损伤、慢性炎症、阿尔茨海默病、衰老和癌症的发病机制有关。蛋白质对铜(II)离子的隔离已被证明可以防止ROS反应的发生。人血清白蛋白N-末端的前四个氨基酸--天冬氨酸-丙氨酸-组氨酸-赖氨酸(DAHK)与铜(II)离子形成一个紧密的结合部位。我们合成了几个类似物，包括对映体d-DAHK，以研究它们在抗坏血酸存在下对铜诱导的羟基自由基和超氧化物生成的影响。D-DAHK可在生理和酸性pH范围(7.5-6.5)内防止硫代巴比妥酸反应物种(TBARS)的形成，并抑制低密度脂蛋白的脂质过氧化。D-DAHK/铜络合物通过显著抑制超氧化物的形成而显示出超氧化物歧化酶的活性。这些体外实验结果表明，d-DAHK可以将铜(II)结合平衡从可交换的铜(II)池转移到紧密结合、不可交换的池，防止ROS的形成，并有可能为ROS相关疾病提供治疗益处。(C)2001年学术出版社。
Copper mobilization and redox activity form damaging reactive oxygen species (ROS) and are implicated in the pathogenesis of ischemia-reperfusion injury, chronic inflammation, Alzheimer's disease, aging, and cancer. Protein sequestration of Cu(II) ions has been shown to prevent ROS-generating reactions. The first four amino acids of the N-terminus of human albumin, Asp-Ala-His-Lys (DAHK), form a tight binding site for Cu(II) ions. We synthesized several analogs, including the enantiomer d-DAHK, to study their effects on copper-induced hydroxyl radical and superoxide formation in the presence of ascorbate. d-DAHK prevented thiobarbituric acid-reactive species (TBARS) formation within physiological and acidic pH ranges (7.5-6.5) and inhibited low-density lipoprotein lipid peroxidation. A d-DAHK/Cu complex exhibited superoxide dismutase-like activity by significantly inhibiting superoxide formation. These in vitro results suggest that d-DAHK may shift the Cu(II)-binding equilibrium from the exchangeable Cu(II) pool to the tightly-bound, nonexchangeable pool, prevent ROS formation, and potentially provide therapeutic benefit for ROS-related diseases. (C) 2001 Academic Press.