Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto del Departamento de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina.
Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Instituto del Departamento de Química Biológica de la Facultad de Ciencias Exactas y Naturales (IQUIBICEN), Departamento de Química Biológica, Facultad de Ciencias Exactas y Naturales, Buenos Aires, Argentina.
Eur J Cell Biol. 2018 Aug;97(6):411-421. doi: 10.1016/j.ejcb.2018.06.002. Epub 2018 Jun 19.
Calcium (Ca) plays an important role in angiogenesis, as it activates the cell migration machinery. Different proangiogenic factors have been demonstrated to induce transient Ca increases in endothelial cells. This has raised interest in the contribution of Ca channels to cell migration, and in a possible use of channel-blocking compounds in angiogenesis-related pathologies. We have investigated the ability of erythropoietin (Epo), a cytokine recently involved in angiogenesis, to induce Ca influx through different types of membrane channels in EA.hy926 endothelial cells. The voltage-dependent Ca channel antagonists amlodipine and diltiazem inhibited an Epo-triggered transient rise in intracellular Ca, similarly to a specific inhibitor (Pyr3) and a blocking antibody against the transient potential calcium channel 3 (TRPC3). Unlike diltiazem, amlodipine and the TRPC3 inhibitors prevented the stimulating action of Epo in cell migration and in vitro angiogenesis assays. Amlodipine was also able to inhibit an increase in endothelial cell migration induced by Epo in an inflammatory environment generated with TNF-α. These results support the participation of Ca entry through voltage-dependent and transient potential channels in Epo-driven endothelial cell migration, highlighting the antiangiogenic activity of amlodipine.
钙（Ca）在血管生成中起着重要作用，因为它激活了细胞迁移机制。已经证明不同的促血管生成因子可诱导内皮细胞中 Ca 的短暂增加。这引起了人们对 Ca 通道对细胞迁移的贡献以及在与血管生成相关的病理中使用通道阻断化合物的可能性的兴趣。我们研究了最近参与血管生成的细胞因子促红细胞生成素（Epo）诱导 EA.hy926 内皮细胞中不同类型膜通道中 Ca 内流的能力。电压依赖性 Ca 通道拮抗剂氨氯地平和地尔硫卓抑制了 Epo 触发的细胞内 Ca 短暂升高，类似于特异性抑制剂（Pyr3）和针对瞬时电位钙通道 3（TRPC3）的阻断抗体。与地尔硫卓不同，氨氯地平和 TRPC3 抑制剂可防止 Epo 在细胞迁移和体外血管生成测定中的刺激作用。在 TNF-α产生的炎症环境中，氨氯地平还能够抑制 Epo 诱导的内皮细胞迁移增加。这些结果支持 Ca 通过电压依赖性和瞬时电位通道进入在 Epo 驱动的内皮细胞迁移中的参与，突出了氨氯地平的抗血管生成活性。
