Short-Term Aldosterone Action on Na,K-ATPase Surface Expression
| Autor: | Marija Zecevic, Vanessa Summa, David Mordasini, Eric Féraille, François Verrey, Dirk Heitzmann, Alain Vandewalle |
|---|---|
| Rok vydání: | 2003 |
| Předmět: |
Epithelial sodium channel
Regulation of gene expression medicine.medical_specialty Aldosterone biology urogenital system Reabsorption General Neuroscience Xenopus biology.organism_classification General Biochemistry Genetics and Molecular Biology chemistry.chemical_compound Endocrinology History and Philosophy of Science chemistry Internal medicine SGK1 medicine Na+/K+-ATPase G alpha subunit |
| Zdroj: | Annals of the New York Academy of Sciences. 986:554-561 |
| ISSN: | 1749-6632 0077-8923 |
| Popis: | Aldosterone controls extracellular volume and blood pressure by regulating Na(+) reabsorption across epithelial cells of the aldosterone-sensitive distal nephron (ASDN). This effect is mediated by a coordinate action on the luminal channel ENaC (generally rate limiting) and the basolateral Na,K-ATPase. Long-term effects of aldosterone (starting within 3 to 6 hours and increasing over days) are mediated by the direct and indirect induction of stable elements of the Na(+) transport machinery (e.g., Na,K-ATPase alpha subunit), whereas short-term effects appear to be mediated by the upregulation of short-lived elements of the machinery (e.g., ENaC alpha subunit) and of regulatory proteins, such as the serum- and glucocorticoid-regulated kinase SGK1. We have recently shown that in cortical collecting duct (CCD) from adrenalectomized (ADX) rats, the increase in Na,K-ATPase activity (approximately threefold in 3 h), induced by a single aldosterone injection, can be fully accounted for by the increase in Na,K-ATPase cell-surface expression. Using the model cell line mpkCCD(cl4), we showed that the parallel increase in Na,K-ATPase function [assessed by Na(+) pump current (I(p)) measurements] and cell-surface expression depends on transcription and translation, and that it is not secondary to a change in apical Na(+) influx. As a first approach to address the question whether the aldosterone-induced regulatory protein SGK1 might play a role in mediating Na,K-ATPase translocation, we have used the Xenopus laevis expression system. SGK1 coexpression indeed increased both the Na(+) pump current and the surface expression of pumps containing the rat alpha1 subunits. In summary, aldosterone controls Na(+) reabsorption in the short term not only by regulating the apical cell-surface expression of ENaC but also by coordinately acting on the basolateral cell-surface expression of the Na,K-ATPase. Results obtained in the Xenopus oocyte expression system suggest the possibility that this effect could be mediated in part by the aldosterone-induced kinase SGK1. |
| Databáze: | OpenAIRE |
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