Inhibition of Na+,K+-ATPase by ouabain triggers epithelial cell death independently of inversion of the [Na+]i/[K+]i ratio

Dmitry Pchejetski, Sebastien Taurin, Shant Der Sarkissian, Olga D Lopina, Alexei V Pshezhetsky, Johanne Tremblay, Denis deBlois, Pavel Hamet, Sergei N Orlov

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54 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)735-44
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume301
Issue number3
Publication statusPublished - 14 Feb 2003

Keywords

  • Animals
  • Calcium
  • Cell Death
  • Cell Line
  • Cell Survival
  • Cycloheximide
  • Dactinomycin
  • Dogs
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors
  • Epithelial Cells
  • Ion Transport
  • Kidney Tubules, Collecting
  • Kinetics
  • Nucleic Acid Synthesis Inhibitors
  • Ouabain
  • Potassium
  • Protein Synthesis Inhibitors
  • Sodium
  • Sodium-Potassium-Exchanging ATPase

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