Sp1 modification of human endothelial nitric oxide synthase promoter increases the hypoxia-stimulated activity

作者：Yang, Yunhua; Liu, Song; Fan, Zhenhua; Li, Zhuo; Liu, Jing^*; Xing, Feiyue

来源：Microvascular Research, 2014, 93: 80-86.

DOI：10.1016/j.mvr.2014.03.004

• GENE-EXPRESSION
• VASCULAR SYSTEM
• TRANSCRIPTIONAL ACTIVATION
• SIGNALING MOLECULE
• ENOS GENE
• CELLS
• FAMILY
• ALPHA
• ATHEROSCLEROSIS
• POLYMORPHISM

Human endothelial nitric oxide synthase (eNOS) gene has a TATA-less weak promoter with a low activity. The aim of this study was to increase eNOS promoter activity by modification. Human eNOS promoter was modified by inserting a Sp1 element at a - 74 bp site and function of the modified promoter was investigated via a hypoxia model induced by cobalt chloride in human umbilical vein endothelial cells. The results demonstrated that the Sp1-modified promoter resulted in a significant increase of normalized luciferase activity in the presence of hypoxia. There was a correlation between the transcriptional activity of the Sp1 -modified promoter and the level of eNOS expression with enhancement of nitric oxide production. Together, these data indicate that human eNOS promoter activity is increased by inserting Sp1 binding site into the GC-rich region of the promoter in response to hypoxia, suggesting that this provides an approach to ameliorate microcirculation barrier of some cardiovascular disease and to study its mechanistic process.

• 出版日期2014-5
• 单位暨南大学