Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10760
Full metadata record
DC FieldValueLanguage
dc.contributor.authorCook, Natashaen
dc.contributor.authorFraser, Scott Aen
dc.contributor.authorKaterelos, Marinaen
dc.contributor.authorKatsis, Frosaen
dc.contributor.authorGleich, Kurten
dc.contributor.authorMount, Peter Fen
dc.contributor.authorSteinberg, Gregory Ren
dc.contributor.authorLevidiotis, Vickien
dc.contributor.authorKemp, Bruce Een
dc.contributor.authorPower, David Anthonyen
dc.date.accessioned2015-05-16T00:18:39Z
dc.date.available2015-05-16T00:18:39Z
dc.date.issued2009-01-28en
dc.identifier.citationAmerican Journal of Physiology. Renal Physiology 2009; 296(4): F801-9en
dc.identifier.govdoc19176702en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/10760en
dc.description.abstractThe energy-sensing kinase AMP-activated protein kinase (AMPK) is associated with the sodium-potassium-chloride cotransporter NKCC2 in the kidney and phosphorylates it on a regulatory site in vitro. To identify a potential role for AMPK in salt sensing at the macula densa, we have used the murine macula densa cell line MMDD1. In this cell line, AMPK was rapidly activated by isosmolar low-salt conditions. In contrast to the known salt-sensing pathway in the macula densa, AMPK activation occurred in the presence of either low sodium or low chloride and was unaffected by inhibition of NKCC2 with bumetanide. Assays using recombinant AMPK demonstrated activation of an upstream kinase by isosmolar low salt. The specific calcium/calmodulin-dependent kinase kinase inhibitor STO-609 failed to suppress AMPK activation, suggesting that it was not part of the signal pathway. AMPK activation was associated with increased phosphorylation of the specific substrate acetyl-CoA carboxylase (ACC) at Ser(79), as well as increased NKCC2 phosphorylation at Ser(126). AMPK activation due to low salt concentrations was inhibited by an adenovirus construct encoding a kinase dead mutant of AMPK, leading to reduced ACC Ser(79) and NKCC2 Ser(126) phosphorylation. This work demonstrates that AMPK activation in macula densa-like cells occurs via isosmolar changes in sodium or chloride concentration, leading to phosphorylation of ACC and NKCC2. Phosphorylation of these substrates in vivo is predicted to increase intracellular chloride and so reduce the effect of salt restriction on tubuloglomerular feedback and renin secretion.en
dc.language.isoenen
dc.subject.otherAMP-Activated Protein Kinases.genetics.metabolismen
dc.subject.otherAcetyl-CoA Carboxylase.metabolismen
dc.subject.otherAnimalsen
dc.subject.otherApoptosis.drug effectsen
dc.subject.otherBenzimidazoles.pharmacologyen
dc.subject.otherBumetanide.pharmacologyen
dc.subject.otherCalcium-Calmodulin-Dependent Protein Kinases.antagonists & inhibitors.metabolismen
dc.subject.otherCell Lineen
dc.subject.otherEnzyme Activationen
dc.subject.otherKidney Tubules.drug effects.enzymology.pathologyen
dc.subject.otherMiceen
dc.subject.otherMutationen
dc.subject.otherNaphthalimides.pharmacologyen
dc.subject.otherNecrosisen
dc.subject.otherOsmolar Concentrationen
dc.subject.otherPhosphorylationen
dc.subject.otherProtein Kinase Inhibitors.pharmacologyen
dc.subject.otherRecombinant Proteins.metabolismen
dc.subject.otherSerineen
dc.subject.otherSodium Chloride.metabolismen
dc.subject.otherSodium Potassium Chloride Symporter Inhibitors.pharmacologyen
dc.subject.otherSodium-Potassium-Chloride Symporters.metabolismen
dc.subject.otherSolute Carrier Family 12, Member 1en
dc.subject.otherTime Factorsen
dc.titleLow salt concentrations activate AMP-activated protein kinase in mouse macula densa cells.en
dc.typeJournal Articleen
dc.identifier.journaltitleAmerican journal of physiology. Renal physiologyen
dc.identifier.affiliationnatasha.cook@austin.org.auen
dc.identifier.affiliationDept. of Nephrology, Austin Health, Studley Rd., Heidelberg 3084, Victoria, Australiaen
dc.identifier.doi10.1152/ajprenal.90372.2008en
dc.description.pagesF801-9en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/19176702en
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.