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AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1
Fraser, Scott A. Choy, Suet-Wan Pastor-Soler, Núria M. Li, Hui Davies, Matthew R. P. Cook, Natasha Katerelos, Marina Mount, Peter F. Gleich, Kurt McRae, Jennifer L.
Fraser, Scott A.
Choy, Suet-Wan
Pastor-Soler, Núria M.
Li, Hui
Davies, Matthew R. P.
Cook, Natasha
Katerelos, Marina
Mount, Peter F.
Gleich, Kurt
McRae, Jennifer L.
Abstract
Salt reabsorption is the major energy-requiring process in the kidney, and AMP-activated protein kinase (AMPK) is an important regulator of cellular metabolism. Mice with targeted deletion of the β1-subunit of AMPK (AMPK-β1−/− mice) had significantly increased urinary Na+ excretion on a normal salt diet. This was associated with reduced expression of the β-subunit of the epithelial Na+ channel (ENaC) and increased subapical tubular expression of kidney-specific Na+-K+-2Cl− cotransporter 2 (NKCC2) in the medullary thick ascending limb of Henle. AMPK-β1−/− mice fed a salt-deficient diet were able to conserve Na+, but renin secretion increased 180% compared with control mice. Cyclooxygenase-2 mRNA also increased in the kidney cortex, indicating greater signaling through the macula densa tubular salt-sensing pathway. To determine whether the increase in renin secretion was due to a change in regulation of fatty acid metabolism by AMPK, mice with a mutation of the inhibitory AMPK phosphosite in acetyl-CoA carboxylase 1 [ACC1-knockin (KI)S79A mice] were examined. ACC1-KIS79A mice on a normal salt diet had no increase in salt loss or renin secretion, and expression of NKCC2, Na+-Cl− cotransporter, and ENaC-β were similar to those in control mice. When mice were placed on a salt-deficient diet, however, renin secretion and cortical expression of cyclooxygenase-2 mRNA increased significantly in ACC1-KIS79A mice compared with control mice. In summary, our data suggest that renin synthesis and secretion are regulated by AMPK and coupled to metabolism by phosphorylation of ACC1.
Keywords
acetyl-CoA carboxylase 1, AMP-activated protein kinase, renin
Date
2010
Type
Journal article
Journal
American Journal of Physiology - Renal Physiology
Book
Volume
305
Issue
5
Page Range
F679-F690
Article Number
ACU Department
Faculty of Health Sciences
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
File Access
Controlled