Biomaterial Database

Salt-induced Na+/K+-ATPase-α/β expression involves soluble adenylyl cyclase in endothelial cells. 2017

Mirja Mewes, and Johanna Nedele, and Katrin Schelleckes, and Olga Bondareva, and Malte Lenders, and Kristina Kusche-Vihrog, and Hans-Joachim Schnittler, and Stefan-Martin Brand, and Boris Schmitz, and Eva Brand

Internal Medicine D, Department of Nephrology, Hypertension and Rheumatology, University Hospital Muenster, Albert-Schweitzer-Campus 1, 48149, Muenster, Germany.

High dietary salt intake may lead to vascular stiffness, which predicts cardiovascular diseases such as heart failure, and myocardial and cerebral infarctions as well as renal impairment. The vascular endothelium is a primary target for deleterious salt effects leading to dysfunction and endothelial stiffness. We hypothesize that the Ca2+- and bicarbonate-activated soluble adenylyl cyclase (sAC) contributes to Na+/K+-ATPase expression regulation in vascular endothelial cells and is an important regulator of endothelial stiffness. In vitro stimulation of vascular endothelial cells with high sodium (150 mM Na+)-induced Na+/K+-ATPase-α and Na+/K+-ATPase-β protein expression determined by western blot. Promoter analyses revealed increased cAMP response element (CRE)-mediated Na+/K+-ATPase-α transcriptional activity under high sodium concentrations. Inhibition of sAC by the specific inhibitor KH7 or siRNA reduced the sodium effects. Flame photometry revealed increased intracellular sodium concentrations in response to high sodium stimulations, which were paralleled by elevated ATP levels. Using atomic force microscopy, a nano-technique that measures cellular stiffness and deformability, we detected significant endothelial stiffening under increased sodium concentrations, which was prevented by inhibition of sAC using KH7 and Na+/K+-ATPase using ouabain. Furthermore, analysis of primary aortic endothelial cells in an in vitro aging model revealed an impaired Na+/K+-ATPase-α sodium response and elevated intracellular sodium levels with cellular aging. We conclude that sAC mediates sodium-induced Na+/K+-ATPase expression in vascular endothelium and is an important regulator of endothelial stiffness. The reactivity of Na+/K+-ATPase-α expression regulation in response to high sodium seems to be impaired in aging endothelial cells and might be a component of endothelial dysfunction.

UI	MeSH Term	Description	Entries
D010042	Ouabain	A cardioactive glycoside consisting of rhamnose and ouabagenin, obtained from the seeds of Strophanthus gratus and other plants of the Apocynaceae; used like DIGITALIS. It is commonly used in cell biological studies as an inhibitor of the NA(+)-K(+)-EXCHANGING ATPASE.	Acocantherin,G-Strophanthin,Acolongifloroside K,G Strophanthin
D004730	Endothelium, Vascular	Single pavement layer of cells which line the luminal surface of the entire vascular system and regulate the transport of macromolecules and blood components.	Capillary Endothelium,Vascular Endothelium,Capillary Endotheliums,Endothelium, Capillary,Endotheliums, Capillary,Endotheliums, Vascular,Vascular Endotheliums
D000254	Sodium-Potassium-Exchanging ATPase	An enzyme that catalyzes the active transport system of sodium and potassium ions across the cell wall. Sodium and potassium ions are closely coupled with membrane ATPase which undergoes phosphorylation and dephosphorylation, thereby providing energy for transport of these ions against concentration gradients.	ATPase, Sodium, Potassium,Adenosinetriphosphatase, Sodium, Potassium,Na(+)-K(+)-Exchanging ATPase,Na(+)-K(+)-Transporting ATPase,Potassium Pump,Sodium Pump,Sodium, Potassium ATPase,Sodium, Potassium Adenosinetriphosphatase,Sodium-Potassium Pump,Adenosine Triphosphatase, Sodium, Potassium,Na(+) K(+)-Transporting ATPase,Sodium, Potassium Adenosine Triphosphatase,ATPase Sodium, Potassium,ATPase, Sodium-Potassium-Exchanging,Adenosinetriphosphatase Sodium, Potassium,Pump, Potassium,Pump, Sodium,Pump, Sodium-Potassium,Sodium Potassium Exchanging ATPase,Sodium Potassium Pump
D000262	Adenylyl Cyclases	Enzymes of the lyase class that catalyze the formation of CYCLIC AMP and pyrophosphate from ATP.	Adenyl Cyclase,Adenylate Cyclase,3',5'-cyclic AMP Synthetase,Adenylyl Cyclase,3',5' cyclic AMP Synthetase,AMP Synthetase, 3',5'-cyclic,Cyclase, Adenyl,Cyclase, Adenylate,Cyclase, Adenylyl,Cyclases, Adenylyl,Synthetase, 3',5'-cyclic AMP
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012964	Sodium	A member of the alkali group of metals. It has the atomic symbol Na, atomic number 11, and atomic weight 23.	Sodium Ion Level,Sodium-23,Ion Level, Sodium,Level, Sodium Ion,Sodium 23
D012965	Sodium Chloride	A ubiquitous sodium salt that is commonly used to season food.	Sodium Chloride, (22)Na,Sodium Chloride, (24)NaCl
D017673	Sodium Chloride, Dietary	Sodium chloride used in foods.	Dietary Sodium Chloride,Table Salt,Chloride, Dietary Sodium,Salt, Table
D042783	Endothelial Cells	Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.	Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell