NOX5 variants are functionally active in endothelial cells
NOX5 variants are functionally active in endothelial cells
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DOI：
10.1016/j.freeradbiomed.2006.10.054
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发表时间：
2007-02-15
影响因子：
7.4
通讯作者：
Goerlach, Agnes
中科院分区：
文献类型：
--
作者：
BelAiba, Rachida S.;Djordjevic, Talija;Goerlach, Agnes
NADPH氧化酶已被确定为血管细胞中活性氧（ROS）的来源。除了最初描述的含有gp 91 phox（NOX 2）的酶外，还鉴定了NOX 2的几种同源物。尽管NOX 1、NOX 2和NOX 4在内皮细胞中表达，但在这些细胞中尚未报道含有不同序列的额外N-末端钙结合结构域的NOX 5的功能作用。在人微血管内皮细胞（HMEC-1）的内质网和血管壁中发现了NOX 5蛋白。HMEC-1细胞表达NOX 5 β和NOX 5 δ以及缺乏钙结合结构域的变体（NOX 5S）。NOX 5 β和NOX 5S增加基础ROS水平。离子霉素专门增强NOX 5 β介导的ROS产生。虽然p22 phox在过表达时与两种NOX 5蛋白相互作用，但它对NOX 5介导的ROS产生不是必需的。NOX 5蛋白刺激内皮细胞增殖和毛细血管样结构的形成，而通过siRNA耗尽NOX 5阻止了对凝血酶的这些反应。这些数据表明，内皮细胞表达不同的NOX 5变体，包括缺乏钙结合结构域的NOX 5S。N 0X 5蛋白是功能性的，促进内皮ROS产生、增殖和毛细血管样结构的形成，并有助于内皮对凝血酶的反应。这些发现表明，NOX 5变体在控制血管系统中的ROS依赖性过程中发挥着新的作用。(c)2006 Elseviey Inc. All rights reserved.
NADPH oxidases have been identified as sources of reactive oxygen species (ROS) in vascular cells. In addition to the initially described enzyme containing gp91phox (NOX2), several homologues to NOX2 have been identified. Whereas NOX1, NOX2, and NOX4 are expressed in endothelial cells, a functional role of NOX5 containing additional N-terminal calcium-binding domains of varying sequences has not been reported in these cells. NOX5 protein was found in the endoplasmic reticulum of human microvascular endothelial cells (HMEC-1) and in the vascular wall. HMEC-1 cells expressed NOX5 beta and NOX5 delta as well as a variant lacking calcium-binding domains (NOX5S). NOX5 beta and NOX5S increased basal ROS levels. lonomycin exclusively enhanced NOX5 beta-mediated ROS production. Although p22phox, when overexpressed, interacted with both NOX5 proteins, it was not essential for NOX5-mediated ROS production. NOX5 proteins stimulated endothelial cell proliferation and the formation of capillary-like structures whereas depletion of NOX5 by siRNA prevented these responses to thrombin. These data show that endothelial cells express different NOX5 variants including NOX5S lacking calcium-binding domains. NOX5 proteins are functional, promoting endothelial ROS production, proliferation, and the formation of capillary-like structures and contribute to the endothelial response to thrombin. These findings suggest that NOX5 variants play a novel role in controlling ROS-dependent processes in the vasculature. (c) 2006 Elseviey Inc. All rights reserved.