Department of Biochemistry and Cell Biology, Vision Research Foundation, Chennai, India.
Birla Institute of Technology & Science, Pilani, India.
Chem Biol Drug Des. 2018 Mar;91(3):797-804. doi: 10.1111/cbdd.13145. Epub 2017 Dec 6.
Angiogenesis is a process of synthesis of new blood vessels from preexisting vasculature. Copper (Cu) as a micronutrient is important to many proteins for their physiological roles. Cu is transported by ceruloplasmin from liver to other parts of the body. Copper transporter 1 (CTR1) is a transmembrane protein which participate in Cu transport across the cell. It is also known to be involved in angiogenesis. In this study, we have designed three peptides from copper-binding regions of CTR1 which are rich in histidine and methionine. These peptides were screened for their inhibitory effect on angiogenesis in the HUVEC model. Mass spectroscopy studies revealed that all the three peptides derived from CTR 1 (Pep 1, 2, and 3) bound to Cu. The intracellular Cu levels estimated by atomic absorption spectroscopy showed decreased levels of copper in peptide-treated cells as compared to control. These peptides inhibited proliferation, migration, and tube formation in HUVEC by sequestering copper, preventing its entry into the cell and thereby inhibiting angiogenesis.
血管生成是从预先存在的脉管系统合成新血管的过程。铜（Cu）作为一种微量营养素，对许多蛋白质的生理功能至关重要。铜通过铜蓝蛋白从肝脏运输到身体的其他部位。铜转运蛋白 1（CTR1）是一种跨膜蛋白，参与细胞内的 Cu 转运。它也被认为与血管生成有关。在这项研究中，我们设计了三个来自 CTR1 的铜结合区域的肽，这些区域富含组氨酸和蛋氨酸。这些肽在 HUVEC 模型中被筛选以抑制血管生成。质谱研究表明，所有三种源自 CTR1 的肽（肽 1、2 和 3）都与 Cu 结合。原子吸收光谱法估计的细胞内 Cu 水平显示，与对照相比，肽处理的细胞中的铜水平降低。这些肽通过螯合铜来抑制 HUVEC 的增殖、迁移和管形成，从而阻止其进入细胞，从而抑制血管生成。
