Soluble adenylyl cyclase in vascular endothelium: Gene expression control of epithelial sodium channel-α, Na+/K+-ATPase-α/β, and mineralocorticoid receptor

Boris Schmitz, Johanna Nedele, Katrin Guske, Martina Maase, Malte Lenders, Michael Schelleckes, Kristina Kusche-Vihrog, Stefan Martin Brand, Eva Brand*

*Korrespondierende/r Autor/-in für diese Arbeit
13 Zitate (Scopus)

Abstract

The Ca2+-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.

OriginalspracheEnglisch
ZeitschriftHypertension
Jahrgang63
Ausgabenummer4
Seiten (von - bis)753-761
Seitenumfang9
ISSN0194-911X
DOIs
PublikationsstatusVeröffentlicht - 04.2014

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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