ERK1/2 controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell of the cortical collecting duct of the mouse kidney.

Détails

ID Serval
serval:BIB_E88DCF4D8C6E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
ERK1/2 controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell of the cortical collecting duct of the mouse kidney.
Périodique
Journal of Biological Chemistry
Auteur(s)
Michlig S., Mercier A., Doucet A., Schild L., Horisberger J.D., Rossier B.C., Firsov D.
ISSN
0021-9258 (Print)
ISSN-L
0021-9258
Statut éditorial
Publié
Date de publication
2004
Peer-reviewed
Oui
Volume
279
Numéro
49
Pages
51002-51012
Langue
anglais
Résumé
The collecting duct of normal kidney exhibits significant activity of the MEK1/2-ERK1/2 pathway as shown in vivo by immunostaining of phosphorylated active ERK1/2 (pERK1/2). The MEK1/2-ERK1/2 pathway controls many different ion transports both in proximal and distal nephron, raising the question of whether this pathway is involved in the basal and/or hormone-dependent transepithelial sodium reabsorption in the principal cell of the cortical collecting duct (CCD), a process mediated by the apical epithelial sodium channel and the basolateral sodium pump (Na,K-ATPase). To answer this question we used ex vivo microdissected CCDs from normal mouse kidney or in vitro cultured mpkCCDcl4 principal cells. Significant basal levels of pERK1/2 were observed ex vivo and in vitro. Aldosterone and vasopressin, known to up-regulate sodium reabsorption in CCDs, did not change ERK1/2 activity either ex vivo or in vitro. Basal and aldosterone- or vasopressin-stimulated sodium transport was down-regulated by the MEK1/2 inhibitor PD98059, in parallel with a decrease in pERK1/2 in vitro. The activity of Na,K-ATPase but not that of epithelial sodium channel was inhibited by MEK1/2 inhibitors in both unstimulated and aldosterone- or vasopressin-stimulated CCDs in vitro. Cell surface biotinylation showed that intrinsic activity rather than cell surface expression of Na,K-ATPase was controlled by pERK1/2. PD98059 also significantly inhibited the activity of Na,K-ATPase ex vivo. Our data demonstrate that the ERK1/2 pathway controls Na,K-ATPase activity and transepithelial sodium transport in the principal cell and indicate that basal constitutive activity of the ERK1/2 pathway is a critical component of this control.
Mots-clé
Aldosterone/metabolism, Animals, Biological Transport, Biotinylation, Blotting, Western, Cell Membrane/metabolism, Cells, Cultured, Dose-Response Relationship, Drug, Electrophysiology, Enzyme Inhibitors/pharmacology, Flavonoids/pharmacology, Kidney/metabolism, Kidney Tubules, Collecting/metabolism, Ligands, Male, Mice, Mitogen-Activated Protein Kinase 1/physiology, Mitogen-Activated Protein Kinase 3/physiology, Nephrons/metabolism, Phosphorylation, Sodium/metabolism, Sodium-Potassium-Exchanging ATPase/chemistry, Sodium-Potassium-Exchanging ATPase/metabolism, Time Factors, Up-Regulation, Vasopressins/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
24/01/2008 13:32
Dernière modification de la notice
20/08/2019 17:11
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