Soluble adenylyl cyclase in vascular endothelium: gene expression control of epithelial sodium channel-α, Na+/K+-ATPase-α/β, and mineralocorticoid receptor
| Autor: | Kristina Kusche-Vihrog, Katrin Guske, Michael Schelleckes, Johanna Nedele, Eva Brand, Boris Schmitz, Malte Lenders, Martina Maase, Stefan-Martin Brand |
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| Rok vydání: | 2014 |
| Předmět: |
Epithelial sodium channel
medicine.medical_specialty Biology Cell Line Adenylyl cyclase chemistry.chemical_compound Mice Mineralocorticoid receptor Vascular Stiffness Internal medicine Internal Medicine Cyclic AMP Response Element-Binding Protein medicine Animals Humans Na+/K+-ATPase Phosphorylation RNA Small Interfering education Protein kinase A Epithelial Sodium Channels Aldosterone Aorta education.field_of_study Soluble adenylyl cyclase CREB-Binding Protein Cell biology Endocrinology Receptors Mineralocorticoid chemistry Gene Expression Regulation Adenylyl Cyclase Inhibitors Models Animal cAMP-dependent pathway Endothelium Vascular Sodium-Potassium-Exchanging ATPase Adenylyl Cyclases Signal Transduction |
| Zdroj: | Hypertension (Dallas, Tex. : 1979). 63(4) |
| ISSN: | 1524-4563 |
| Popis: | The Ca 2+ - and bicarbonate-activated soluble adenylyl cyclase (sAC) has been identified recently as an important mediator of aldosterone signaling in the kidney. Nuclear sAC has been reported to stimulate cAMP response element–binding protein 1 phosphorylation via protein kinase A, suggesting an alternative cAMP pathway in the nucleus. In this study, we analyzed the sAC as a potential modulator of endothelial stiffness in the vascular endothelium. We determined the contribution of sAC to cAMP response element–mediated transcriptional activation in vascular endothelial cells and kidney collecting duct cells. Inhibition of sAC by the specific inhibitor KH7 significantly reduced cAMP response element–mediated promoter activity and affected cAMP response element–binding protein 1 phosphorylation. Furthermore, KH7 and anti-sAC small interfering RNA significantly decreased mRNA and protein levels of epithelial sodium channel-α and Na + /K + -ATPase-α. Using atomic force microscopy, a nano-technique that measures stiffness and deformability of living cells, we detected significant endothelial cell softening after sAC inhibition. Our results suggest that the sAC is a regulator of gene expression involved in aldosterone signaling and an important regulator of endothelial stiffness. Additional studies are warranted to investigate the protective action of sAC inhibitors in humans for potential clinical use. |
| Databáze: | OpenAIRE |
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