Differential expression of EDF-1 and endothelial nitric oxide synthase by proliferating, quiescent and senescent microvascular endothelial cells
Differential expression of EDF-1 and endothelial nitric oxide synthase by proliferating, quiescent and senescent microvascular endothelial cells
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DOI：
10.1016/j.bbamcr.2005.06.013
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发表时间：
2005-09-10
影响因子：
5.1
通讯作者：
Maier, JAM
中科院分区：
文献类型：
--
作者：
Bernardini, D;Ballabio, E;Maier, JAM
内皮分化相关因子（EDF）-1是一种低分子量多肽，在暴露于HIV-1-达特或佛波醇酯TPA的内皮细胞中下调。EDF-1在细胞质中作为钙调蛋白结合蛋白，在细胞核中作为转录辅激活因子。在这里，我们发现EDF-1在非增殖微血管内皮细胞中下调。事实上，静止和衰老都会降低EDF-1的水平，这是由于蛋白酶体的蛋白质降解。我们还描述了一个不同的亚细胞定位EDF-1，主要是核衰老1G 11细胞。由于（i）内皮一氧化氮（NO）似乎在内皮细胞增殖中起作用，并且（ii）NO是参与控制血管张力、炎症反应和血管生成的重要介质，值得注意的是，衰老下调微血管内皮细胞中内皮一氧化氮合酶（eNOS）的表达和活性。相反，静止不影响NOS的表达和活性。微血管内皮细胞中EDF-1的调节可能为老年人血管生成和微血管功能障碍的分子事件提供新的见解。(c)2005 Elsevier B. V.保留所有权利。
Endothelial Differentiation-related Factor (EDF)-1 is a low molecular weight polypeptide downregulated in endothelial cells exposed to HIV-1-Tat or the phorbol ester TPA. EDF-1 acts in the cytosol as a calmodulin binding protein, and in the nucleus as a transcriptional coactivator. Here, we show that EDF-1 is downregulated in non-proliferating microvascular endothelial cells. Indeed, both quiescence and senescence reduce the levels of EDF-1 and this is due to protein degradation through the proteasome. We also describe a different subcellular localization of EDF-1 which is mainly nuclear in senescent 1G11 cells. Since (i) endothelial nitric oxide (NO) seems to play a role in endothelial proliferation and (ii) NO is an important mediator involved in the control of vascular tone, inflammatory responses and angiogenesis, it is noteworthy that senescence downregulates the expression and the activity of endothelial nitric oxide synthase (eNOS) in microvascular endothelial cells. On the contrary, quiescence does not affect NOS expression and activity. The modulation of EDF-1 in microvascular endothelial cells might offer new insights into the molecular events involved in angiogenesis and in microvascular dysfunctions in the elderly. (c) 2005 Elsevier B.V. All rights reserved.