Document Detail

Inhibition of Na+,K+-ATPase by ouabain triggers epithelial cell death independently of inversion of the [Na+]i/[K+]i ratio.
MedLine Citation:
PMID:  12565842     Owner:  NLM     Status:  MEDLINE    
Treatment with ouabain led to massive death of principal cells from collecting ducts (C7-MDCK), indicated by cell swelling, loss of mitochondrial function, an irregular pattern of DNA degradation, and insensitivity to pan-caspase inhibitor. Equimolar substitution of extracellular Na(+) by K(+) or choline(+) sharply attenuated the effect of ouabain on intracellular Na(+) and K(+) content but did not protect the cells from death in the presence of ouabain. In contrast to ouabain, inhibition of the Na(+)/K(+) pump in K(+)-free medium increased Na(+)(i) content but did not affect cell survival. In control and K(+)-free medium, ouabain triggered half-maximal cell death at concentrations of approximately 0.5 and 0.05 microM, respectively, which was consistent with elevation of Na(+)/K(+) pump sensitivity to ouabain in K(+)-depleted medium. Our results show for the first time that the death of ouabain-treated renal epithelial cells is independent of the inhibition of Na(+)/K(+) pump-mediated ion fluxes and the [Na(+)](i)]/[K(+)](i) ratio.
Dimitri Pchejetski; Sebastien Taurin; Shant Der Sarkissian; Olga D Lopina; Alexei V Pshezhetsky; Johanne Tremblay; Denis deBlois; Pavel Hamet; Sergei N Orlov
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  301     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2003 Feb 
Date Detail:
Created Date:  2003-02-04     Completed Date:  2003-04-14     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  735-44     Citation Subset:  IM    
Centre de recherche, Centre hospitalier de l'Université de Montréal, Hôtel-Dieu, PQ, Canada
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MeSH Terms
Calcium / physiology
Cell Death
Cell Line
Cell Survival / drug effects
Cycloheximide / pharmacology
Dactinomycin / pharmacology
Dose-Response Relationship, Drug
Enzyme Inhibitors / pharmacology*
Epithelial Cells / chemistry,  cytology,  drug effects,  enzymology
Ion Transport
Kidney Tubules, Collecting / chemistry,  cytology*,  enzymology*
Nucleic Acid Synthesis Inhibitors / pharmacology
Ouabain / pharmacology*
Potassium / analysis
Protein Synthesis Inhibitors / pharmacology
Sodium / analysis
Sodium-Potassium-Exchanging ATPase / antagonists & inhibitors*
Reg. No./Substance:
0/Enzyme Inhibitors; 0/Nucleic Acid Synthesis Inhibitors; 0/Protein Synthesis Inhibitors; 50-76-0/Dactinomycin; 630-60-4/Ouabain; 66-81-9/Cycloheximide; 7440-09-7/Potassium; 7440-23-5/Sodium; 7440-70-2/Calcium; EC ATPase

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

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