Almaca, Joana and Kongsuphol, Patthara and Hieke, Bernhard and Ousingsawat, Jiraporn and Viollet, Benoit and Schreiber, Rainer and Amaral, Margarida D. and Kunzelmann, Karl (2009) AMPK controls epithelial Na+ channels through Nedd4-2 and causes an epithelial phenotype when mutated. PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 458 (4). pp. 713-721. ISSN 0031-6768, 1432-2013
Full text not available from this repository. (Request a copy)Abstract
The metabolic sensor adenosine-monophosphate-activated kinase (AMPK) detects the cellular energy status and adjusts metabolic activity according to the cytosolic AMP to ATP ratio. Na+ absorption by epithelial Na+ channels (ENaC) is a highly energy-consuming process that is inhibited by AMPK. We show that the catalytic subunit alpha 1 of AMPK inhibits ENaC in epithelial tissues from airways, kidney, and colon and that AMPK regulation of ENaC is absent in AMPK alpha 1-/- mice. These mice demonstrate enhanced electrogenic Na+ absorption that leads to subtle changes in intestinal and renal function and may also affect Na+ absorption and mucociliary clearance in the airways. We demonstrate that AMPK uses the ubiquitin ligase Nedd4-2 to inhibit ENaC by increasing ubiquitination and endocytosis of ENaC. Thus, enhanced expression of epithelial Na+ channels was detected in colon, airways, and kidney of AMPK alpha 1-/- mice. Therefore, AMPK alpha 1 is a physiologically important regulator of electrogenic Na+ absorption and may provide a novel pharmacological target for controlling epithelial Na+ transport.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ACTIVATED PROTEIN-KINASE; SODIUM-CHANNEL; TRANSPORT; CELLS; INHIBITION; AMPK; AMPK alpha 1; ENaC; Epithelial Na+ channel; Knockout |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 10 Sep 2020 08:44 |
| Last Modified: | 10 Sep 2020 08:44 |
| URI: | https://pred.uni-regensburg.de/id/eprint/28665 |
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