Ouabain-induced perturbations in intracellular ionic homeostasis regulate death receptor-mediated apoptosis

Mihalis I. Panayiotidis, Rodrigo Franco, Carl D. Bortner, John A. Cidlowski

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The Na+-K+-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function have been suggested to be associated with apoptosis. We report here that the Na+-K+-ATPase inhibitor ouabain, potentiates apoptosis in the human lymphoma Jurkat cells exposed to Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not other apoptotic agents such as H2O2, thapsigargin or UV-C implicating a role for the Na+-K+-ATPase in death receptor-induced apoptosis. Interestingly, ouabain also potentiated perturbations in cell Ca2+ homeostasis only in conjunction with the apoptotic inducer FasL but not TRAIL. Ouabain did not affect alterations in the intracellular Ca2+ levels in response to H2O2, thapsigargin or UV-C. FasL-induced alterations in Ca2+ were not abolished in Ca2+-free medium but incubation of cells with BAPTA-AM inhibited both Ca2+ perturbations and the ouabain-induced potentiation of FasL-induced apoptosis. Our data suggest that the impairment of the Na+-K+-ATPase activity during apoptosis is linked to perturbations in cell Ca2+ homeostasis that modulate apoptosis induced by the activation of Fas by FasL.

Original languageEnglish (US)
Pages (from-to)834-849
Number of pages16
Issue number7
StatePublished - Jul 2010


  • Apoptosis
  • Apoptotic volume decrease
  • Calcium
  • Fas ligand
  • Na-k-Atpase
  • Ouabain

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science
  • Clinical Biochemistry
  • Cell Biology
  • Biochemistry, medical
  • Cancer Research


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