File(s) under permanent embargo
AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1
journal contribution
posted on 2013-09-01, 00:00 authored by Scott A Fraser, Suet-Wan Choy, Núria M Pastor-Soler, Hui Li, Matthew R P Davies, Natasha Cook, Marina Katerelos, Peter F Mount, Kurt Gleich, Jennifer L McRae, Karen DwyerKaren Dwyer, Bryce J W van Denderen, Kenneth R Hallows, Bruce E Kemp, David A PowerSalt 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-KI(S79A) 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-KI(S79A) 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.
History
Journal
American journal of physiology. Renal physiologyVolume
305Issue
5Pagination
F679 - F690Publisher
American Physiological SocietyLocation
Bethesda, Md.Publisher DOI
ISSN
0363-6127eISSN
1522-1466Language
engPublication classification
C1 Refereed article in a scholarly journalCopyright notice
2013, American Physiological SocietyUsage metrics
Keywords
AMP-activated protein kinaseacetyl-CoA carboxylase 1reninAMP-Activated Protein KinasesAcetyl-CoA CarboxylaseAnimalsEpithelial Sodium ChannelsMicePhosphorylationSodiumSodium Chloride, DietaryScience & TechnologyLife Sciences & BiomedicinePhysiologyUrology & NephrologyACTIVATED PROTEIN-KINASECL COTRANSPORTER NKCC2SODIUM-CHANNEL ENACSERUM TOTAL RENINSURFACE EXPRESSIONEPITHELIAL-CELLSUPSTREAM KINASEOBESE-PATIENTSENERGY SENSORPhysiology
Licence
Exports
RefWorks
BibTeX
Ref. manager
Endnote
DataCite
NLM
DC