Related Experiment Video
Updated: May 21, 2026

En Face Detection of Nitric Oxide and Superoxide in Endothelial Layer of Intact Arteries
Published on: February 25, 2016
Phytoestrogen genistein up-regulates endothelial nitric oxide synthase expression via activation of cAMP response
Hongwei Si1, Jie Yu, Hongling Jiang
1Department of Human Nutrition, Foods, and Exercise, College of Agriculture and Life Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA.
Abstract:
We previously reported that genistein, a phytoestrogen, up-regulates endothelial nitric oxide synthase (eNOS) and prevents hypertension in rats that are independent of estrogen signaling machinery. However, how genistein regulates eNOS expression is unknown. In the present study, we show that genistein enhanced eNOS expression and NO synthesis in primary human aortic endothelial cells. Inhibition of extracellular signal regulated kinase, phosphoinositol-3 kinase, or protein kinase C did not affect genistein-enhanced eNOS expression and NO synthesis. However, chemical inhibition of protein kinase A (PKA) or adenoviral transfer of the specific endogenous PKA inhibitor gene completely abolished PKA activity and genistein-stimulated eNOS expression and NO production. Accordingly, genistein induced PKA activity and subsequent phosphorylation of cAMP response element (CRE)-binding protein (CREB) at Ser133. Suppression of CREB by small interfering RNA transfection abolished genistein-enhanced eNOS expression and NO production. Consistently, deletion of the CRE site within human eNOS promoter eliminated genistein-stimulated eNOS promoter activity. These findings provide the first evidence to our knowledge that genistein may play a beneficial role in vascular function through targeting the PKA/CREB/eNOS/NO signaling pathway.
More Related Videos
08:32Application of Genetically Encoded Fluorescent Nitric Oxide (NO•) Probes, the geNOps, for Real-time Imaging of NO• Signals in Single Cells
Published on: March 16, 2017
06:18An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Related Concept Videos
Nitric Oxide Signaling Pathway
Regulation of Angiogenesis and Blood Supply
GPCRs Regulate Adenylyl Cylase Activity
Two...
Transducer Mechanism: Enzyme-Linked Receptors
Major types that are helpful drug targets include:
Paracrine Signaling
Cell Specific Gene Expression