Combined cupric- and cuprous-binding peptides are effective in preventing IL-8 release from endothelial cells and redox reactions
Combined cupric- and cuprous-binding peptides are effective in preventing IL-8 release from endothelial cells and redox reactions
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DOI：
10.1016/j.bbrc.2007.03.182
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发表时间：
2007-06-01
影响因子：
3.1
通讯作者：
Bar-Or, David
中科院分区：
文献类型：
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作者：
Rael, Leonard T.;Rao, Nagaraja K. R.;Bar-Or, David
铜的动员和随后的氧化还原反应与许多炎症性疾病的发病机制有关。铜离子（Cu2+）还原为亚铜离子（Cu+）是铜诱导活性氧（ROS）产生的必要条件。设计了结合Cu2+和Cu+并具有阻止铜氧化还原反应能力的肽。barC下的DAHGMTCA (N)和barC下的DAHKGMTCA (N)在铜/抗坏血酸溶液中以1:1的肽/铜比有效地阻止硫代巴比妥酸反应物质（TBARS）的形成。这是在含有这些肽的铜/抗坏血酸溶液的还原电位中观察到的，基于氧化还原电位（ORP）测量，还原电位为1:1。在barC下，肽DAHGMTCA (R)在2:1的比例下有效，但在1:1的比例下不有效，氧化电位增加。这表明带正电的氨基酸，如Cu+结合基序中的精氨酸(R)干扰了金属螯合。所有测试的肽都能有效地阻止12-肉豆蔻酸13-醋酸磷(PMA)/铜刺激的人脐静脉内皮细胞（HUVEC）释放IL-8。使用Cu+/Cu2+结合肽可能有助于治疗与铜相关的ros相关疾病。(c) 2007爱思唯尔公司版权所有。
Copper mobilization and subsequent redox reactions have been implicated in the pathogenesis of numerous inflammation-based diseases. Reduction of the cupric ion (Cu2+) to the cuprous ion (Cu+) is necessary for the production of copper-induced reactive oxygen species (ROS). Peptides, designed to bind both Cu2+ and Cu+ and have the ability to prevent copper redox reactions, were studied. The peptides DAHGMTCA (N) under barC and DAHKGMTCA (N) under barC were effective at preventing the formation of thiobarbituric acid-reactive species (TBARS) in a copper/ascorbate solution at a 1:1 peptide/Cu ratio. This was observed in the reducing potential of the copper/ascorbate solutions containing these peptides at a 1:1 ratio based on oxidation-reduction potential (ORP) measurements. The peptide DAHGMTCA (R) under barC was effective at a 2:1 ratio, but not at a 1:1 ratio in which an increase in the oxidation potential was observed. This suggests that a positively charged amino acid such as arginine (R) in the Cu+-binding motif interferes with metal chelation. All peptides tested were effective at preventing IL-8 release from phorbol 12-myristate 13-acetate (PMA)/copper-stimulated human umbilical vein endothelial cells (HUVEC). The use of Cu+/Cu2+-binding peptides might be beneficial in the treatment of ROS-related diseases associated with copper. (c) 2007 Elsevier Inc. All rights reserved.