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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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

X Zhou1, G Jiang, A Zhao

  • 1Division of Nephrology, Uniformed Services University, Bethesda, Maryland 20814, USA. xiazhou@usuhs.mil

Biochemical and Biophysical Research Communications
|July 5, 2001
PubMed

Insights

Ouabain, a Na,K-ATPase inhibitor, protects kidney cells from apoptosis by activating PI3 kinase. This pathway is crucial for the cell-survival effects of inhibiting Na,K-ATPase.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Renal Physiology

Background:

  • Na,K-ATPase is a critical ion pump in renal proximal tubules.
  • Ouabain is a specific inhibitor of Na,K-ATPase.
  • Apoptosis, or programmed cell death, can be triggered by various cellular stressors.

Purpose of the Study:

  • To investigate the role of PI3 kinase (Phosphatidylinositol 3-kinase) activation in the anti-apoptotic effects of ouabain.
  • To determine if inhibiting Na,K-ATPase activity generally confers cytoprotection.
  • To elucidate the signaling pathway linking Na,K-ATPase inhibition to cell survival.

Main Methods:

  • LLC-PK1 cells (porcine renal proximal tubular cell line) were used.
  • Apoptosis was induced using actinomycin D (Act D).
  • PI3 kinase activity, Akt phosphorylation, and cytoprotective effects were assessed.
  • PI3 kinase was inhibited using wortmannin and LY294002.

Main Results:

  • Ouabain attenuated Act D-induced apoptosis in a dose-dependent manner.
  • Low potassium (K+) medium, reducing Na,K-ATPase activity, also showed anti-apoptotic effects.
  • Both ouabain and low K+ medium increased PI3 kinase activity and Akt phosphorylation.
  • PI3 kinase inhibition reversed the cytoprotective effects of ouabain.

Conclusions:

  • Inhibition of Na,K-ATPase activates PI3 kinase in LLC-PK1 cells.
  • Activated PI3 kinase mediates the anti-apoptotic and cytoprotective effects.
  • This pathway highlights a novel mechanism for renal cell protection.

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