Document Detail

Acid increases NHE8 surface expression and activity in NRK cells.
MedLine Citation:
PMID:  22088432     Owner:  NLM     Status:  MEDLINE    
We previously demonstrated that there is a paucity of brush-border membrane NHE3 in neonates, the predominant Na(+)/H(+) exchanger in the adult proximal tubule, while NHE8 is relatively highly expressed in neonates compared with adults. We recently showed that metabolic acidosis in neonatal rodents can increase brush-border membrane NHE8 protein expression and Na(+)/H(+) exchange activity. To further examine the regulation of NHE8 by acid, we incubated NRK cells, which express NHE8 but not NHE3, with either acid or control media (6.6 vs. 7.4). There was an increase in Na(+)/H(+) exchanger activity within 6 h of incubation with acid media assessed as the rate of sodium-dependent recovery of pH from an acid load (dpH(i)/dt). The acid stimulation persisted for at least 24 h. The increase in Na(+)/H(+) exchange activity was paralleled by an increase in surface expression of NHE8, assessed by surface biotinylation and streptavidin precipitation. The increase in both apical membrane NHE8 protein expression and Na(+)/H(+) exchange activity with pH 6.6 media compared with 7.4 media was not affected by actinomycin D or cycloheximide consistent with an increase in surface expression independent of mRNA or protein synthesis. Furthermore, there was no increase in total cellular NHE8 protein abundance or mRNA abundance with acid media. Finally, we demonstrate that the increase in surface expression of NHE8 with acid media was blocked by colchicine and cytochalasin D and mediated by acid increasing the rate of exocytosis. In conclusion, NHE8 surface expression and activity are regulated by acid media by increasing the rate of trafficking to the apical membrane.
Catherine Joseph; Katherine Twombley; Jyothsna Gattineni; Qiuyu Zhang; Vangipuram Dwarakanath; Michel Baum
Publication Detail:
Type:  Journal Article     Date:  2011-11-16
Journal Detail:
Title:  American journal of physiology. Renal physiology     Volume:  302     ISSN:  1522-1466     ISO Abbreviation:  Am. J. Physiol. Renal Physiol.     Publication Date:  2012 Feb 
Date Detail:
Created Date:  2012-02-08     Completed Date:  2012-04-23     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  100901990     Medline TA:  Am J Physiol Renal Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  F495-503     Citation Subset:  IM    
Dept. of Pediatrics, U.T. Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9063, USA.
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MeSH Terms
Cell Line
Cells, Cultured
Hydrogen-Ion Concentration
Kidney Tubules, Proximal / cytology,  metabolism*
Microvilli / metabolism
Sodium-Hydrogen Antiporter / genetics,  metabolism*
Reg. No./Substance:
0/NHE8 protein, rat; 0/Sodium-Hydrogen Antiporter

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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