Inhibition of NA, K-ATPase activates PI3 kinase and inhibits apoptosis in LLC-PK1 cells

Xiaoming Zhou*, Guisen Jiang, Aiping Zhao, Tzvetanka Bondeva, Przemyslaw Hirszel, Tamas Balla

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

60 Scopus citations


In the present study we used LLC-PK1 cells, a porcine renal proximal tubular cell line, to investigate whether PI3 kinase activation was involved in the anti-apoptotic effect of ouabain, a specific inhibitor of Na,K-ATPase. Apoptosis was induced by actinomycin D (Act D, 5 μM) and assessed by appearance of hypodiploid nuclei and DNA fragmentation. Ouabain attenuated Act D-induced apoptotic response in a dose-dependent manner. Incubation in a low K+ medium (0.1 mM) which is another way to decrease Na,K-ATPase activity also had anti-apoptotic effect. Both ouabain and low K+ medium increased the PI3 kinase activity in p85 immunoprecipitates. Ouabain, as well as incubation in the low K+ medium, also increased the phosphorylation of Akt. Inhibition of PI3 kinase by either wortmannin or LY294002 reversed the cytoprotective effect of ouabain. These data together indicate that inhibition of Na,K-ATPase activates PI3 kinase in LLC-PK1 cells which could then exert the cytoprotective effect.

Original languageEnglish
Pages (from-to)46-51
Number of pages6
JournalBiochemical and Biophysical Research Communications
Issue number1
StatePublished - 2001
Externally publishedYes


  • Actinomycin D
  • Akt
  • Apoptosis
  • LLC-PK1 cells
  • Na,K-ATPase
  • Ouabain
  • PI3 kinase
  • Potassium


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