Abstract
The primary means of intestinal absorption of nutrients by villus cells is via Na-dependent nutrient co-transporters located in the brush border membrane (BBM). These secondary active co-transport processes require a favorable transcellular Na gradient that is provided by Na-K-ATPase. In chronic enteritis, malabsorption of essential nutrients is partially due to inhibition of villus Na-K-ATPase activity mediated by specific immune inflammatory mediators that are known to be elevated in the inflamed mucosa. However, how Prostaglandin E2 (PGE2), a specific mediator of nutrient malabsorption in the villus BBM, may mediate the inhibition of Na-K-ATPase is not known. Therefore, this study aimed to determine the effect of PGE2 on Na-K-ATPase in villus cells and define its mechanism of action. In vitro, in IEC-18 cells, PGE2 treatment significantly reduced Na-K-ATPase activity, accompanied by a significant increase in the intracellular levels of cyclic Adenosine Monophosphate (cAMP). The treatment with cAMP analog 8-Bromo-cAMP mimicked the PGE2-mediated effect on Na-K-ATPase activity, while Rp-cAMP (PKA inhibitor) pretreatment reversed the same. The mechanism of inhibition of PGE2 was secondary to a transcriptional reduction in the Na-K-ATPase α1 and β1 subunit genes, which was reversed by the Rp-cAMP pretreatment. Thus, the PGE2-mediated activation of the PKA pathway mediates the transcriptional inhibition of Na-K-ATPase activity in vitro.
Highlights
Na-K-ATPase is an integral plasma membrane protein present in the basolateral membrane (BLM) of epithelial cells and transports 3 Na out of and 2 K into the cell by utilizing one adenosine triphosphate (ATP) per transport cycle
As a consequence of pumping Na out of the cell, Na-K-ATPase generates a favorable transcellular Na gradient required for Na-dependent nutrient absorption in the brush border membrane (BBM) of the intestinal epithelial cells
IEC-18 cells were treated with various concentrations of Prostaglandin E2 (PGE2) for 24 h, and the activity of Na-K-ATPase was measured by 86Rb+ uptake
Summary
Na-K-ATPase is an integral plasma membrane protein present in the basolateral membrane (BLM) of epithelial cells and transports 3 Na out of and 2 K into the cell by utilizing one ATP per transport cycle. As a consequence of pumping Na out of the cell, Na-K-ATPase generates a favorable transcellular Na gradient required for Na-dependent nutrient absorption in the brush border membrane (BBM) of the intestinal epithelial cells. Three distinct subunits: alpha (α), beta (β), and gamma (γ) constitute a fully functional Na-K-ATPase enzyme. The regulatory β subunit facilitates maturation of the α subunit by forming an α/β heterodimer and transporting this enzyme to the plasma membrane [2]. Of these isoforms α1 and β1 are ubiquitously present in intestinal mucosa [5,6]. The activity of Na-K-ATPase can be regulated by various mechanisms: (1) trafficking of pump from cytoplasm to the plasma membrane [7], (2) transcriptional regulation of subunits [8,9], and (3) phosphorylation and dephosphorylation of subunits [10,11,12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
