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

Pchejetski, Dmitry, Taurin, Sebastien, Der Sarkissian, Shant, Lopina, Olga D., Pshezhetsky, Alexei V., Tremblay, Johanne, deBlois, Denis, Hamet, Pavel and Orlov, Sergei N. (2003) Inhibition of Na+,K+-ATPase by ouabain triggers epithelial cell death independently of inversion of the [Na+]i/[K+]i ratio. Biochemical and Biophysical Research Communications, 301 (3). pp. 735-744. ISSN 0006-291X

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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.

Item Type: Article
Uncontrolled 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
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 16 Dec 2014 10:12
Last Modified: 08 Sep 2023 13:30
DOI: 10.1016/S0006-291X(02)03002-4

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